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>> GOOD MORNING, NIH.

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GOOD MORNING.

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I AM NINA SHORE IESM THE DEPUTY

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DIRECTOR FOR INTRAMURAL RESEARCH

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AND TODAY IT IS MY DISTINCT

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PLEASURE TO INTRODUCE THE 2024

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PHILLIP S. CHEN JR. Ph.D.

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DISTINGUISHED LECTURER

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DR. STEPHEN WHITEHEAD AND TO

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WELCOME TO TO NIH DR.   DR. PH P

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CHEN.

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>> FIRST A NOTE, THE
LECTURE ON

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INNOVATION AND TECHNOLOGY

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TRANSFER WAS ESTABLISHED IN 2006

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BY THE NIH DEPUTY DIRECTOR FOR

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INTRAMURAL RESEARCH AND THE NIH

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OFFICE FOR TECHNOLOGY TRANSFER.

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ON THE OCCASION OF DR. CHEN'S

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RETIREMENT, AFTER OVER 41 YEARS

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OF SERVICE TO THE NIH, THE

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LECTURESHIP HONORED DR. CHEN'S

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REMARKABLE DIVERSE AND CREATIVE

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CONTRIBUTIONS TO THE NIH AND

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ESPECIALLY TO ITS INTRAMURAL

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RESEARCH PROGRAM AND TO THE

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FIELD OF TECHNOLOGY TRANSFER.

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DR. CHEN RECEIVED HIS Ph.D. IN

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PHARMAICOLOGY FROM THE

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UNIVERSITY OF  ROCHESTER.

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DURING HIS DISTINGUISHED CAREER

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AT NIH, HE SERVED UNDER 8 NIH

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DIRECTORS AND HELD SCIENTIFIC

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AND LEADERSHIP POSITIONS IN 2

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INSTITUTES, 1 DIVISION AND THE

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OFFICE OF THE DIRECTOR.

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IN 1986 DR. CHEN ESTABLISHED THE

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NIH OFFICE OF TECHNOLOGY

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TRANSFER TO IMPLEMENT THE

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PROVISION OF THE FEDERAL

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TECHNOLOGY TRANSFER ACT.

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HE FORMULATED THE GUIDING

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PRINCIPLES UPON WHICH TECHNOLOGY

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TRANSFER FUNCTIONS TODAY

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INCLUDING AS MANY OF THE

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AUDIENCE WILL REALIZE THE

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SIGNIFICANCE OF THIS, INCLUDING

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CREATING THE COOPERATIVE

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RESEARCH AND DEVELOPMENT

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AGREEMENT FONDLY KNOWN AS THE

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CREDA.

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ABOVE ALL, DR. CHEN OFFERED

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NIHERS WISE, TRUSTED AND

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COMPASSIONATE COUNCIL AND THIS

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EARNED HIM THE RESPECT,

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ADMIRATION AND GRADDITUDE OF

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BOTH OF THE SCIENTIFIC AND THE

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ADMINISTRATIVE COMMUNITIES AT

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NIH.

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TODAY'S SPEAKER AND THE 2024

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RECIPIENT OF THE CHEN

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LECTURESHIP IS DR. TEFEN 

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W--STEPHEN WHITEHEAD, HE VEEFED

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HIS MASTERS FROM BRIGHAM YOUNG

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YESTERDAY AND HIS Ph.D. FROM

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OREGONITATE UNIVERSITY.

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HE JOINED NIAID 29 YEARS AGO AS

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A POST DOCTORAL FELLOW HE IS

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CURRENTLY A SENIOR INVESTIGATOR

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IN THE LABORATORY OF VIRAL DECS

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AT NIAID.

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HIS RESEARCH IS FOCUSED ON THE

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DEVELOPMENT AND EVALUATION OF

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VACCINE CANDIDATES FOR DENG UE

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AND OTHER VECTOR BORN DISEASES.

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OVER THE COURSE OF THESE

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PROJECTS HE HAS DEVELOPED

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VARIOUS LIFE ATTENUATE VACCINE

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CANDIDATES WITH A LEAD

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TETRAVALENTINEDDENT DENG UE

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CANDIDATE CURRENTLY COMPLETING

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PHASE 3 CLINICAL EVALUATION IN

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BRAZIL.

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IN 2018 HE WAS HONORED WITH THE

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AMERICAN SOCIETY FOR

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MICROBIOLOGIES MORRIS HILLAMAN

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AWARD AND HE IS THE INVENTOR IN

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OVER 10 PATENT GROUPS AND THE

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DENG UE VIRUS TECHNOLOGY HAS

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BEEN LICENSED AROUND THE WORLD

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TO 8 PHARMACEUTICAL COMPANIES IN

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AN EFFORT TO CONTROL DENGUE

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DISEASE.

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>> PLEASE JOIN US IN
WELCOMING

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WITH OUR SPEAKER AND THEN PLEASE

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JOIN US FOR A RECEPTION IN THE

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LIBRARY FOLLOWING THE LECTURE. 

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THANK YOU.

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[ APPLAUSE ]

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>> THANK YOU, I AM VERY
PLEASED

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TO BE HERE TO GIVE THIS LECTURE

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TO HONOR DR. CHEN AND ALL OF THE

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CHAMPIONSHIP HE HAS FOR TECH

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TRANSFER BECAUSE AS WE WILL

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DISCUSS TECH TRANSFER MATTERS

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AND THIS WOULD NOT BE POSSIBLE

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WITHOUT THE HELP OF THOSE

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OFFICES.

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LET ME BEIMIN BRIEFLY BY SAYING,

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WE WILL TALK ABOUT AN ARTHROPOD

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BORN VIRUS, SPECIFICALLY DENGUE

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VIRUS, ARGT O VIRUSES, THE ARGT

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O POD SIDE IS MOSQUITOES TICKS

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AND FLIES, VIRUS SIDE IS

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DIFFERENT FLAVI VIRUSES, ALPHA

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VIRUSES, BUNUA VIRUSES AND

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HERE'S A LIST OF THE MEDICALLY

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IMPORTANT VIRUSES.

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IT IS REGRETTABLE THAT YOU

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MECHANIZE MANY OF THEM BECAUSE

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THEY'RE ALL STILL AROUND, OKAY

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IN YOU WILL--YOU KNOW DENGUE

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VIRUS, ZIKA VIRUS, YOU ARE

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HEARING ABOUT MYO VIRUS,

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UNFORTUNATELY YOU'RE LEARNING

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ABOUT VENEZUELANS EQUINE VIRUS,

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IF YOU HAVEN'T ALREADY, YOU WILL

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HEAR ABOUT ORAPUSH VIRUS, A

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BUNYA VIRUS THAT IS REEMERGING.

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A RESPONSE TO THOSE INFECTIONS

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INCLUDES PRIMARY TREATMENT AND

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CARE CENTERS, THAT IS THE TOP OF

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THE LIST THEN WE HAVE SACK

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SEENS, WE HAVE VECTOR CONTROL

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AND REPELLANTS. 

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WE HAVE A FEW THAT ARE IN

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DEVELOPMENT, THERAPEUTICS

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ANTIVIRALS, SOME OF THESE

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VIRUSES WE'VE LEARNED ON

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SEXUALLY TRANSMITTED SO WE CAN

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CONTROL THE DAMAGE FROM THOSE

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VIRUSES USING CONDOMS AND BIRTH

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CONTROL.

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AS WE LEARNED FROM ZIKA VIRUS,

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THERE ARE TRAVEL RESTRICTIONS

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AND SCREENINGS THAT GO ON, WE

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ARE CHECKING THE BLOOD SUPPLY

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FOR MANY OF THESE AND THERE MAY

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BE OTHERS THAT NEED TO COME

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FORWARD.

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SOME OF THE CHALLENGES FOR

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DEVELOPING VACCINES TO THESE ARE

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THAT MOST OF THE ARBOVIRUS

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INFECTIONS MOST LOW OCCUR IN

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THESE SHORT LIVED EPIDEMICS, THE

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EXCEPTION OF COURSE BEING DENGUE

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VIRUS WHICH IS ALWAYS WITH US.

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THIS LOW DISEASE INCIDENCE MAKE

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ITS VERY DIFFICULT TO DO

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EFFICACY TRIALS FOR VACCINES AND

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YOU KNOW, THESE ARE SHORT

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SPORADIC OUTBREAKS, BY THE TIME

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YOU HAVE A VACCINE CANDIDATE

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READY AND YOU'RE READY TO TEST

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IT, THE VIRUS HAS MOVED ON, IT'S

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NO LONGER CIRCULATING.

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IT'S HARD TO PREDICT WHAT THE

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NEXT OUTBREAK WILL BE AND YOU

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KNOW MANY OF THESE ARE WHAT WE

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CALL ORPHAN VACCINES, THEY'RE

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NOT PROFITABLE INVESTMENTS FOR

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PHARMACEUTICAL COMPANIES.

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SO THAT'S A DIFFICULT AND THEN

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THERE'S ALWAYS THIS WIDE GAP

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BETWEEN CLINICAL DISCOVERY AND

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EVALUATION WHICH IS ILLUSTRATED

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HERE AS YOU MOVE FROM BENCH TO

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BEDSIDE, THE VALLEY OF DEATH FOR

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MANY VACCINES IS AS WE GET INTO

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THESE CLINICAL TRIALS.

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BUT EVEN ONCE YOU'VE INITIATED A

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CLINICAL TRIAL, AND THIS IS

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WHERE TECH TRANSFER COMES IN,

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YOU NEED AN IMPLEMENTATION

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SCHEME OR PROGRAM.

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THIS NEEDS TO MOVE FORWARD INTO

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A PHARMACEUTICAL COMPANIES THAT

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CAN PRODUCE A VACCINE.

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NOW THIS BENCH TO BODY SIDE TO

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IMPLEMENTATION CAN TAKE A

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CONSIDERABLE AMOUNT OF TIME AND

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SO YOU CAN SEE THESE VARIOUS

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VACCINES ON THE LEFT, GENERALLY

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7, 8, 9, YEARS FROM BEGINNING TO

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APPROVAL.

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THE EXCEPTION IS ON THE BOTTOM,

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SANOFI PASTOR AND SEVERAL OTHER

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COMPANIES BEGAN WORKING ON WHAT

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THEN BECAME THE DENG VAXIA, IN

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1971 WITH DIFFERENT VERSION OF

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THE PLATFORM, IT TOOK THEM 44

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YEARS.

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NOW TONGUE IN CHECK, AND I SAID

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BECAUSE IT'S OF COURSE IT'S 44

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YEARS, BECAUSE IT'S FOR A ZACH

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SEEN AND 10 YEARS FOR EACH

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VACCINE.

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THE DENGUE VIRUS WE'RE TALKING

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ABOUT TODAY IMPORTANTLY COMES IN

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4 DISTINCT SEROTYPES.

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IT'S A SINGLE STRAPPEDDED

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POSITIVE SENSE RNA VIRUS, 4

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DISTINCT SEROTYPES, REALLY MEAN

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4 DISTINCT VIRUSES, THEY REALLY

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ARE VERY DIFFERENT.

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THEY ACT VERY DIFFERENTLY IN

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MOST ASSAYS AND MOST

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INVESTIGATIONS.

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IMPORTANT IN THIS SLIDE IS THE

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ENVELOPE PROTEIN ON THE OUTSIDE

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OF THE VIRUS PARTICLE, THAT IS

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THE TARGET FOR NEUTRALIZING

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ANTIBODY.

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ALL OF THESE NONSTRUCTURAL

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PROTEINS, THE MAIORITY OF THE

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GENOME ARE--HAVE DIFFERENT

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REPLICATION FUNCTIONS BUT THEY

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ARE THE PROTEINS THAT CONTAIN

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MOST OF THE T-CELL EPITOPES THAT

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ARE RECOGNIZED.

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THIS IS WHERE YOU FIND DENGUE.

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THREE BILLION PEOPLE LIVE IN

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THIS ZONE WHERE YOU HAVE

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FREQUENT OR SPORADIC OUTBREAKS

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OF DENGUE.

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IT'S FAIRLY OLD DATA FROM 2013,

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ESTIMATED 390 MILLION ANNUAL

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INFECTIONS, ABOUT A HUNDRED

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MILLION OF THEM ARE CLINICALLY

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APPARENT.

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BUT IT'S IMPORTANT TO NOTE THAT

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DENGUE IS BOTH AN ESTABLISHED

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DEC, AND AN EMERGING AND

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REEMERGING DISEASE.

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THIS IS WHAT DENGUE DISEASE

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LOOKS LIKE, THE DENGUE

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CLASSIFICATION YOU ARE GOING TO

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HAVE THE MAJORITY OF INFECTIONS

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LEAD TO A SYMPTOM ADIC

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INFECTIONS, SOME OF THEM ARE

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DENGUE WITHOUT WARNING SIGNS

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ISSUES THOSE ARE GBL LYE

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UNREPORTED.

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AS YOU MOVE UP THE PYRAMID, HAVE

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YOU A SMALL PERCENTAGE THAT HAVE

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THESE WARNING SIGNS LISTED AND

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THEN SOME WITH SEVERE DENGUE.

257
00:10:58,317 --> 00:10:59,285
OKAY?

258
00:10:59,285 --> 00:11:00,786
FORTUNATELY WITH PROPER

259
00:11:00,786 --> 00:11:01,821
MANAGEMENT, THE CASE FATALITY

260
00:11:01,821 --> 00:11:05,424
RATE IS PROBABLY LESS THAN HALF

261
00:11:05,424 --> 00:11:06,225
A PERCENT.

262
00:11:06,225 --> 00:11:10,563
BUT THAT IS WITH PROPER CASE

263
00:11:10,563 --> 00:11:12,631
MANAGEMENT SO IF I WERE TO COME

264
00:11:12,631 --> 00:11:14,233
DOWN WITH SERIOUS DENGUE, I

265
00:11:14,233 --> 00:11:17,770
WOULD WANT TO BE TREATED BY

266
00:11:17,770 --> 00:11:22,441
BRIDGET WILSON IN VIETNAM OR

267
00:11:22,441 --> 00:11:29,482
MAKE DR. LAKAMARA IN SRI LANKA.

268
00:11:29,482 --> 00:11:30,816
THEY ARE VERY GOOD.

269
00:11:30,816 --> 00:11:32,685
THEY DON'T HAVE FATAL CASES.

270
00:11:32,685 --> 00:11:34,787
MOST OF THE PEOPLE YOU ENCOUNTER

271
00:11:34,787 --> 00:11:37,756
ON THE STREET OF SOUTHEAST ASIA,

272
00:11:37,756 --> 00:11:40,059
BANGKOK FOR EXAMPLE ARE IMMUNE

273
00:11:40,059 --> 00:11:41,727
TO ALL 4 DENGUE SEROTYPES, THE

274
00:11:41,727 --> 00:11:43,195
QUESTION IS HOW DID THEY GET

275
00:11:43,195 --> 00:11:43,696
THAT WAY?

276
00:11:43,696 --> 00:11:46,699
AND THE WAY THEY GET THAT WAY IS

277
00:11:46,699 --> 00:11:49,034
BY SEQUENTIAL EXPOSURE TO

278
00:11:49,034 --> 00:11:50,202
DIFFERENT DENGUE SEROTYPES,

279
00:11:50,202 --> 00:11:51,937
REMEMBER, THERE'S 4 SEROTYPES,

280
00:11:51,937 --> 00:11:53,105
THEY ENCOUNTER THESE AT

281
00:11:53,105 --> 00:11:55,241
DIFFERENT TIMES IN THEIR LIFE

282
00:11:55,241 --> 00:11:58,377
BEGINNING IN CHILDHOOD, SO HERE

283
00:11:58,377 --> 00:12:01,847
IS ADULT A FROM A STUDY WE DID,

284
00:12:01,847 --> 00:12:04,116
PREVACCINATION, YOU CAN SEE THEY

285
00:12:04,116 --> 00:12:06,352
HAVE--THIS PERSON HAS REALLY

286
00:12:06,352 --> 00:12:08,420
GOOD NEUTRALIZING ANTIBODIES TO

287
00:12:08,420 --> 00:12:09,321
ALL 4 SEROTYPES.

288
00:12:09,321 --> 00:12:10,589
THIS IMPORTANT DOESN'T NEED

289
00:12:10,589 --> 00:12:10,923
VACCINATION.

290
00:12:10,923 --> 00:12:14,560
ON THE OTHER SIDE, HERE'S A

291
00:12:14,560 --> 00:12:17,096
CHILD BEFORE VACCINATION HAD NO

292
00:12:17,096 --> 00:12:19,598
DENGUE ANTIBODIES, WE CALL THEM

293
00:12:19,598 --> 00:12:23,769
DENGUE NAIVE, PULSE VACCINATION,

294
00:12:23,769 --> 00:12:25,304
VERY GOOD IMMUNE RESPONSE.

295
00:12:25,304 --> 00:12:27,907
SO THIS IS WHAT NATURAL IMMUNITY

296
00:12:27,907 --> 00:12:28,641
LOOKS LIKE.

297
00:12:28,641 --> 00:12:30,609
CAN WE SAFELY INDUCE THIS

298
00:12:30,609 --> 00:12:31,343
IMMUNITY IN CHILDREN IS THIS AND

299
00:12:31,343 --> 00:12:34,914
THE WAY YOU WOULD DO THAT IS

300
00:12:34,914 --> 00:12:36,515
EITHER THROUGH SIMULTANEOUS

301
00:12:36,515 --> 00:12:37,316
TETRAVALENTINEDDENT VACCINATION,

302
00:12:37,316 --> 00:12:40,319
GIVING ALL 4 SEROTYPES AT ONCE

303
00:12:40,319 --> 00:12:50,029
OR POSSIBLY SEQUENTIAL

304
00:12:50,029 --> 00:12:51,163
VACCINATION.

305
00:12:51,163 --> 00:12:55,701
THIS IS HOW SEQUENTIAL

306
00:12:55,701 --> 00:12:56,168
VACCINATION WORKS.

307
00:12:56,168 --> 00:12:58,837
WE TESTED THIS IN THE CLINIC,

308
00:12:58,837 --> 00:13:00,973
2-7 YEARS LATER WE RECALLED THE

309
00:13:00,973 --> 00:13:02,608
VOLUNTEERS WHO GOT THE VACCINE

310
00:13:02,608 --> 00:13:03,776
AND GAVE THEM DENGUE 1.

311
00:13:03,776 --> 00:13:06,712
WE WANTED ON TO SEE WHAT THE

312
00:13:06,712 --> 00:13:07,313
NEUTRALIZING ANTIBODIES LOOK

313
00:13:07,313 --> 00:13:11,217
LIKE EMPLOY SO HERE ON DAY 0,

314
00:13:11,217 --> 00:13:13,519
WHEN WE HAD RECALLED THESE

315
00:13:13,519 --> 00:13:15,054
INDIVIDUALS READY TO GIVE THEM

316
00:13:15,054 --> 00:13:17,890
DENGUE 1, THESE FOLKS STILL HAD

317
00:13:17,890 --> 00:13:20,059
SOME ANTIBODY TO DENGUE 4.

318
00:13:20,059 --> 00:13:23,829
NO ANTIBODY FOR 2 AND 3.

319
00:13:23,829 --> 00:13:25,097
AFTER WE ADMINISTERED DENGUE 1,

320
00:13:25,097 --> 00:13:28,867
WE SEE THIS NICE BOOST IN DENGUE

321
00:13:28,867 --> 00:13:31,637
4 NEUTRALIZING ANTIBODY TITERS,

322
00:13:31,637 --> 00:13:32,404
PRIMARY IMMUNIZATION TO DENGUE

323
00:13:32,404 --> 00:13:32,538
1.

324
00:13:32,538 --> 00:13:33,772
THIS IS WHAT YOU WOULD EXPECT

325
00:13:33,772 --> 00:13:36,642
EMPLOY BUT WE ALSO SEE THESE

326
00:13:36,642 --> 00:13:38,077
NICE ANTIBODY TITERS TO DENGUE 2

327
00:13:38,077 --> 00:13:39,311
AND 3.

328
00:13:39,311 --> 00:13:40,546
THESE INDIVIDUALS HAVE NEVER

329
00:13:40,546 --> 00:13:43,515
SEEN DENGUE 2 AND 3 BUT THEY

330
00:13:43,515 --> 00:13:45,517
HAVE THIS CROSS PROTECTIVE WHAT

331
00:13:45,517 --> 00:13:49,088
WE CALL HETEROTYPIC ANTIBODY TO

332
00:13:49,088 --> 00:13:49,755
THE SEROTYPES.

333
00:13:49,755 --> 00:13:51,890
SEQUENTIAL EXPOSURE TO DENGUE

334
00:13:51,890 --> 00:13:52,825
ILLICITS CROSS REACTIVE

335
00:13:52,825 --> 00:13:53,525
ANTIBODIES BUT YOU HAVE TO CAN

336
00:13:53,525 --> 00:13:56,061
ISSUES WHAT IS THE QUALITY OF

337
00:13:56,061 --> 00:13:57,796
THESE CROSS PROTECTIVE

338
00:13:57,796 --> 00:13:59,598
ANTIBODIES?

339
00:13:59,598 --> 00:14:00,165
ARE THEY PROTECTIVE?

340
00:14:00,165 --> 00:14:02,368
YOU ALSO HAVE TO ASK, YOU KNOW

341
00:14:02,368 --> 00:14:04,036
ONCE I'VE BEEN EXPOSED TO 1

342
00:14:04,036 --> 00:14:05,604
SEROTYPE, WHAT IS THE

343
00:14:05,604 --> 00:14:07,873
CONSEQUENCE OF HAVING THIS

344
00:14:07,873 --> 00:14:11,510
ANTIBODY PROFILE AND THE

345
00:14:11,510 --> 00:14:13,545
CONSEQUENCE IS FAIRLY SEVERE.

346
00:14:13,545 --> 00:14:15,948
YOU CAN HAVE A ANTIBODY

347
00:14:15,948 --> 00:14:17,916
DEPENDENT ENHANCEMENT OF YOUR

348
00:14:17,916 --> 00:14:20,286
DENGUE INFECTION.

349
00:14:20,286 --> 00:14:22,454
PREEXISTING IMMUNITY TO 1 DENGUE

350
00:14:22,454 --> 00:14:24,290
SEROTYPE REALLY IS THE GREATEST

351
00:14:24,290 --> 00:14:26,992
RISK FACTOR FOR A MORE SEVERE

352
00:14:26,992 --> 00:14:27,893
INFECTION, MORE SEVERE DISEASE

353
00:14:27,893 --> 00:14:30,195
WHEN YOU GET YOUR SECOND

354
00:14:30,195 --> 00:14:30,496
INFECTION.

355
00:14:30,496 --> 00:14:32,464
THE WAY THIS WORKS IS, YOU HAVE

356
00:14:32,464 --> 00:14:34,500
IT HETEROGENEOUS OR O TYPIC

357
00:14:34,500 --> 00:14:36,702
ANTIBODY FROM YOUR PREVIOUS

358
00:14:36,702 --> 00:14:38,203
INFECTION, THE NEW INCOMING

359
00:14:38,203 --> 00:14:39,738
VIRUS, BINDS TO THESE

360
00:14:39,738 --> 00:14:41,340
ANTIBODIES, BUT THEY'RE NOT

361
00:14:41,340 --> 00:14:45,177
NEUTRALIZED SO THESE ARE BINDING

362
00:14:45,177 --> 00:14:45,978
NONNEUTRALLIZING ANTIBODIES,

363
00:14:45,978 --> 00:14:48,147
THIS ANTIBODY VIRUS COMPLEX,

364
00:14:48,147 --> 00:14:50,349
THEN HAS ACCESS TO FC GAMMA

365
00:14:50,349 --> 00:14:53,919
RECEPTOR CELLS SUCH AS

366
00:14:53,919 --> 00:14:54,953
MONOCYTES, MORE INTERACTION

367
00:14:54,953 --> 00:14:56,922
MEANS MORE INFECTION, MORE

368
00:14:56,922 --> 00:14:59,325
INFECTION MEANS AN INCREASED

369
00:14:59,325 --> 00:15:00,626
VIRUS LOAD, IT'S HYPOTHESIZED

370
00:15:00,626 --> 00:15:05,097
THIS LEADS TO AN INCREASE IN NS

371
00:15:05,097 --> 00:15:06,699
1 PRODUCTION, INCREASED VASEIO

372
00:15:06,699 --> 00:15:08,934
PERM ANLT MORE DISEASE.

373
00:15:08,934 --> 00:15:12,771
THIS IS ASPECT DEPENDENT AND HAS

374
00:15:12,771 --> 00:15:13,005
BEEN.

375
00:15:13,005 --> 00:15:15,607
THIS IS WHY PARTIAL IMMUNITY TO

376
00:15:15,607 --> 00:15:16,942
DENGUE IS DANGEROUS.

377
00:15:16,942 --> 00:15:21,947
WHAT WE MEDE IS A VACCINE THAT

378
00:15:21,947 --> 00:15:22,681
CAN PROVIDE VACCINE

379
00:15:22,681 --> 00:15:23,015
TETRAIMMUNITY.

380
00:15:23,015 --> 00:15:24,950
IN THE EARLY DAYS OF LABORATORY

381
00:15:24,950 --> 00:15:26,685
INFECT YOWZ DISEASE, WE DECIDED

382
00:15:26,685 --> 00:15:30,589
TO DEVELOP A LIVE ATTENUATE

383
00:15:30,589 --> 00:15:32,257
DENGUE VACCINE.

384
00:15:32,257 --> 00:15:32,424
WHY?

385
00:15:32,424 --> 00:15:34,126
ROBERT CHANIC THOUGHT IT WAS A

386
00:15:34,126 --> 00:15:34,827
GOOD IDEA.

387
00:15:34,827 --> 00:15:37,229
BRIAN MURPHY THOUGHT IT WAS A

388
00:15:37,229 --> 00:15:38,564
GOOD IDEA.

389
00:15:38,564 --> 00:15:41,266
THE WHOLE LAB THOUGHT IT WAS A

390
00:15:41,266 --> 00:15:41,533
GOOD IDEA.

391
00:15:41,533 --> 00:15:43,068
I JUST WANT TO PONT OUT SOME OF

392
00:15:43,068 --> 00:15:47,039
THE INDIVIDUALS IN THIS, JOE

393
00:15:47,039 --> 00:15:47,740
[INDISCERNIBLE], CHRIS HANSEN

394
00:15:47,740 --> 00:15:49,975
STILL WITH THE OFFICE OF THE

395
00:15:49,975 --> 00:15:51,577
DIRECTOR IN DIR AND BRIAN MURPHY

396
00:15:51,577 --> 00:15:53,479
THERE IN THE CENTER GIVING A

397
00:15:53,479 --> 00:15:54,813
VERY STERN LOOK.

398
00:15:54,813 --> 00:15:57,216
THIS IS HOW WE STARTED AND THE

399
00:15:57,216 --> 00:15:59,518
REASON DEVELOPING A LIVE

400
00:15:59,518 --> 00:16:00,552
ATTENUATE VACCINE MADE SOME

401
00:16:00,552 --> 00:16:02,888
SENSE WAS BECAUSE IT HAD BEEN

402
00:16:02,888 --> 00:16:06,191
SUCCESSFUL FOR OTHER FLAVI

403
00:16:06,191 --> 00:16:11,463
VIRUSES, FOR YELLOW FEVER VIRUS,

404
00:16:11,463 --> 00:16:15,567
FOR JAPANESE ENSEVILLE O VIRUS,

405
00:16:15,567 --> 00:16:17,202
THE ANTIGENS AND EPITOPES YOU

406
00:16:17,202 --> 00:16:19,104
DON'T HAVE TO WORRY IF THEY ARE

407
00:16:19,104 --> 00:16:20,472
DESTROYED IN ACTIVATION, THEY

408
00:16:20,472 --> 00:16:22,741
ARE PRESENTED IN THEIR NATIVE

409
00:16:22,741 --> 00:16:24,076
CONFIRMATION, YOU ARE GENERALLY

410
00:16:24,076 --> 00:16:25,611
EXPECTED TO HAVE LIFE LONG

411
00:16:25,611 --> 00:16:26,812
IMMUNITY ESPECIALLY IF YOU'RE

412
00:16:26,812 --> 00:16:27,980
LIVING IN AN ENDEMIC AREA WHERE

413
00:16:27,980 --> 00:16:31,116
YOU CAN BE BOOSTED WHEN YOU'RE

414
00:16:31,116 --> 00:16:31,550
SUSCEPTIBLE.

415
00:16:31,550 --> 00:16:33,352
THEY CAN BE VERY INEXPENSIVE TO

416
00:16:33,352 --> 00:16:35,988
PRODUCE, I WILL TELL YOU WE

417
00:16:35,988 --> 00:16:39,358
PRODUCE OUR VIRUSES A TENTH OF

418
00:16:39,358 --> 00:16:42,461
THE 7 PFU IN TISSUE CULTURE WE

419
00:16:42,461 --> 00:16:43,962
ADMINISTER THEM AT 10 TO THE 3.

420
00:16:43,962 --> 00:16:46,865
SO EVERY ML IS THEY--THE

421
00:16:46,865 --> 00:16:48,700
KRETICALLY 10,000 DOSES, A FLASK

422
00:16:48,700 --> 00:16:50,302
OF CELLS WITH DENGUE CAN BE

423
00:16:50,302 --> 00:16:54,206
ABOUT A MILLION DOSES.

424
00:16:54,206 --> 00:16:55,140
THEY'RE HIGHLY IMMUNOGENIC, AS

425
00:16:55,140 --> 00:16:57,342
YOU WOULD EXPECT FOR A LIVE

426
00:16:57,342 --> 00:17:01,513
ATTENUATE VACCINE, THEY ONLY

427
00:17:01,513 --> 00:17:02,314
REQUIRE 1 DOSE.

428
00:17:02,314 --> 00:17:04,450
THIS IS WHAT I BELIEVE MOST

429
00:17:04,450 --> 00:17:06,618
PEOPLE DON'T APPRECIATE ABOUT

430
00:17:06,618 --> 00:17:08,554
LIVE VACCINES.

431
00:17:08,554 --> 00:17:10,722
FOR LIVE VACCINES, INFECTION IS

432
00:17:10,722 --> 00:17:12,458
REQUIRED FOR IMMUNE STIMULATION.

433
00:17:12,458 --> 00:17:15,227
YOU HAVE TO BE INFECTED.

434
00:17:15,227 --> 00:17:17,729
THE VIRUS NEEDS TO REPLICATE.

435
00:17:17,729 --> 00:17:18,530
THERE'S NOT ENOUGH ANDROGEN

436
00:17:18,530 --> 00:17:19,932
ROUGH ATOM IMENNIC LOAD IN THAT

437
00:17:19,932 --> 00:17:22,201
VACCINE TO DO ANYTHING IF THAT

438
00:17:22,201 --> 00:17:23,535
VIRUS ISN'T GOING TO REPLICATE.

439
00:17:23,535 --> 00:17:26,205
AND YOU CAN LOOK AT THIS

440
00:17:26,205 --> 00:17:27,773
REPLICATION BY LOOKING IN THE

441
00:17:27,773 --> 00:17:29,641
BLOOD FOR THE VIRUS LOAD, FROM

442
00:17:29,641 --> 00:17:31,844
THE VACCINE EITHER BY DIRECT

443
00:17:31,844 --> 00:17:33,812
CULTURE OR RTPC R, CAN YOU LOOK

444
00:17:33,812 --> 00:17:35,347
AT IMMUNITY WHETHER IT'S

445
00:17:35,347 --> 00:17:37,316
ANTIBODY OR T-CELL IMMUNITY, YOU

446
00:17:37,316 --> 00:17:41,820
CAN LOOK AT EVEN SOME OF THE

447
00:17:41,820 --> 00:17:44,189
CLINICAL SIDE EFFECTS OF THAT

448
00:17:44,189 --> 00:17:44,723
VACCINATION.

449
00:17:44,723 --> 00:17:50,195
BUT TO BE AN EFFECTIVE, LIVE,

450
00:17:50,195 --> 00:17:53,165
TETRAVALENT VACCINE ALL FOR

451
00:17:53,165 --> 00:17:55,067
SEROTYPE COMPONENTS NEED TO

452
00:17:55,067 --> 00:17:55,534
REPALATELICATE.

453
00:17:55,534 --> 00:17:56,935
THAT IS THE FOUNDATION FOR

454
00:17:56,935 --> 00:17:59,705
DEVELOPING THE NIH VACCINE.

455
00:17:59,705 --> 00:18:02,875
NOW I ASK THED QUESTION, IS IT

456
00:18:02,875 --> 00:18:06,812
REALLY THIS SIMPLE? 

457
00:18:06,812 --> 00:18:07,880
WOULD VIRUS REPLICATION--VACCINE

458
00:18:07,880 --> 00:18:10,749
REPLICATION BE A CORLATTIVE

459
00:18:10,749 --> 00:18:11,350
PROTECTION?

460
00:18:11,350 --> 00:18:11,717
I BELIEVE IT IS.

461
00:18:11,717 --> 00:18:14,019
AGAIN, TO BE A

462
00:18:14,019 --> 00:18:14,653
TETRAVALENTINEDDENT VACCINE, ALL

463
00:18:14,653 --> 00:18:15,654
4 NEED TO REPLICATE.

464
00:18:15,654 --> 00:18:19,124
HERE ARE THE LIVE ATTENUATE

465
00:18:19,124 --> 00:18:21,360
VACCINES THAT HAVE BEEN

466
00:18:21,360 --> 00:18:23,562
DEVELOPED OVER THE LAST 20

467
00:18:23,562 --> 00:18:25,030
YEARS.

468
00:18:25,030 --> 00:18:27,232
THERE'S A SANOFI PASTOR AT

469
00:18:27,232 --> 00:18:30,235
CANNED WHAT AND TB003 WHICH WE

470
00:18:30,235 --> 00:18:36,642
CALL THE NIH VACCINE OR NOW WE

471
00:18:36,642 --> 00:18:39,077
CALL IT THE BOTONDV, YOU CAN SEE

472
00:18:39,077 --> 00:18:40,312
THESE ARE IN DIFFERENT NUMBER OF

473
00:18:40,312 --> 00:18:43,482
DOSES, THIS IS THE PLATFORM FOR

474
00:18:43,482 --> 00:18:45,951
THESE VACCINES.

475
00:18:45,951 --> 00:18:51,957
FOR THE SANOFI VACCINE, DENG

476
00:18:51,957 --> 00:18:53,725
VAXAI, ALL VIRUS BACKBONE AND

477
00:18:53,725 --> 00:18:55,527
THEY SUBSIDIARY CONSTITUTE IN

478
00:18:55,527 --> 00:18:56,662
THE SUBITUTE PROTEINS FROM

479
00:18:56,662 --> 00:18:57,696
DENGUE 1, 2, 3, 4.

480
00:18:57,696 --> 00:19:01,800
SO THIS IS A VACCINE BACKBONE

481
00:19:01,800 --> 00:19:03,368
EXPRESSING THE ANTIGENS FOR

482
00:19:03,368 --> 00:19:06,471
DENGUE 1, 2, 3, 4.

483
00:19:06,471 --> 00:19:09,341
FOR TAKEDA, IT WAS ATTENUATE

484
00:19:09,341 --> 00:19:11,076
DENGUE 2 BACKBONE AND THEN AGAIN

485
00:19:11,076 --> 00:19:13,178
THEY MADE THESE CHIMERIC VIRUSES

486
00:19:13,178 --> 00:19:15,414
IN WHICH DENGUE 1, 3, 4 ARE

487
00:19:15,414 --> 00:19:17,382
EXPRESSED AND HERE'S THE NIH

488
00:19:17,382 --> 00:19:18,850
VACCINE, KIND OF A COMBINATION

489
00:19:18,850 --> 00:19:19,751
OF THESE DIFFERENT EFFORTS AND

490
00:19:19,751 --> 00:19:22,721
WE WILL TALK MORE ABOUT THAT.

491
00:19:22,721 --> 00:19:25,557
SO, WHAT ABOUT THE EFFICACY AND

492
00:19:25,557 --> 00:19:34,366
THE LONG-TERM SAFETY OF THE

493
00:19:34,366 --> 00:19:36,735
SANOFI DENG VAXIA, RACKINATION

494
00:19:36,735 --> 00:19:39,004
OCCURRED DURING THE YEAR,

495
00:19:39,004 --> 00:19:40,572
VACCINATION EVERY 6 MONTHS, A

496
00:19:40,572 --> 00:19:42,374
YEAR OF EFFICACY ANALYSIS AND

497
00:19:42,374 --> 00:19:45,243
THEN YEAR 3 SAFETY. 

498
00:19:45,243 --> 00:19:46,745
AND THIS IS WHERE THEY RECOGNIZE

499
00:19:46,745 --> 00:19:49,648
THE FIRST PROBLEM WITH THIS

500
00:19:49,648 --> 00:19:50,048
VACCINE.

501
00:19:50,048 --> 00:19:51,950
SO IN INDIVIDUALS WHO ARE

502
00:19:51,950 --> 00:19:53,251
VACCINATED WHO ARE

503
00:19:53,251 --> 00:19:54,453
SERO-NEGATIVE, YOU HAD A

504
00:19:54,453 --> 00:19:56,188
REGGATIVE RISK OF

505
00:19:56,188 --> 00:19:57,289
HOSPITALIZATION GREATER THAN 1.

506
00:19:57,289 --> 00:19:59,725
WHEN YOU BROKE THIS DOWN BY

507
00:19:59,725 --> 00:20:00,892
DIFFERENT ANAL GROUPS, THESE

508
00:20:00,892 --> 00:20:03,295
KIDS THAT WERE 2-5 IN THEIR

509
00:20:03,295 --> 00:20:05,998
STUDY HAD A 7 FOLD HIGHER RISK

510
00:20:05,998 --> 00:20:08,133
OF HOSPITALIZATION ON THEIR NEXT

511
00:20:08,133 --> 00:20:08,767
EXPOSURE TO DENGUE.

512
00:20:08,767 --> 00:20:11,470
SO THIS WAS A BIT OF A RED FLAG.

513
00:20:11,470 --> 00:20:15,374
WAS THIS A SURPRISE?

514
00:20:15,374 --> 00:20:15,674
IT WAS.

515
00:20:15,674 --> 00:20:17,409
TO MANY OF US WE ALREADY KNEW

516
00:20:17,409 --> 00:20:20,512
THIS WAS A RATHER IMBALANCED

517
00:20:20,512 --> 00:20:20,879
VACCINE.

518
00:20:20,879 --> 00:20:23,015
HERE'S DATA IN NAIVE SUBJECTS

519
00:20:23,015 --> 00:20:24,583
VACCINATED WITH 3 DOSES.

520
00:20:24,583 --> 00:20:26,418
AFTER THE VERY FIRST DOSE, THIS

521
00:20:26,418 --> 00:20:30,355
IS WHAT THE NEUTRALIZING

522
00:20:30,355 --> 00:20:31,490
ANTIBODY TITERS LOOK LIKE.

523
00:20:31,490 --> 00:20:33,959
AND YOU CAN SEE IT'S CLEARLY

524
00:20:33,959 --> 00:20:35,727
DOMINATED BY DENGUE 4.

525
00:20:35,727 --> 00:20:37,763
THERE'S A 70 FOLD DIFFERENCE

526
00:20:37,763 --> 00:20:39,164
BETWEEN THE ANTIBODY RESPONSE

527
00:20:39,164 --> 00:20:42,200
BETWEEN DENGUE 1 AND DENGUE 4.

528
00:20:42,200 --> 00:20:44,136
THEY GIVE A SECOND DOSE, DENGUE

529
00:20:44,136 --> 00:20:46,204
4 ANTIBODIES CONTINUE TO WANE AS

530
00:20:46,204 --> 00:20:48,507
EXPECTED, SO YOU DON'T SEE A

531
00:20:48,507 --> 00:20:50,208
BOOST, I SUPPOSE ALL OF THIS

532
00:20:50,208 --> 00:20:52,778
DENGUE 4 IN THE SECOND DOSE WAS

533
00:20:52,778 --> 00:20:54,046
COMPLETELY NEUTRALIZED FROM THE

534
00:20:54,046 --> 00:20:55,914
FIRST DOSE, MAYBE A LITTLE BIT

535
00:20:55,914 --> 00:20:58,116
OF ANTIBODY FOR DENGUE 1, 2, 3.

536
00:20:58,116 --> 00:21:00,552
BUT REALLY IT'S PRINCIPALLY A

537
00:21:00,552 --> 00:21:03,321
DENGUE 4 VACCINE, IT'S NOT

538
00:21:03,321 --> 00:21:03,622
BOOSTED.

539
00:21:03,622 --> 00:21:06,858
DENGUE 1, 2, 3, RESPONSES

540
00:21:06,858 --> 00:21:07,159
IN

541
00:21:07,159 --> 00:21:10,162
INCREASE A LITTLE BIT BUT DOES

542
00:21:10,162 --> 00:21:11,630
THIS IMBALANCED IMMUNE RESPONSE

543
00:21:11,630 --> 00:21:12,964
LEAD TO VARIABLE EFFICACY AND

544
00:21:12,964 --> 00:21:13,532
INDEED IT DID.

545
00:21:13,532 --> 00:21:18,870
SO WHEN THEY LOOK AT EFFICACY IN

546
00:21:18,870 --> 00:21:20,706
LATIN AMERICA, SO HERE'S ANOTHER

547
00:21:20,706 --> 00:21:22,708
NUMBER OF DENGUE CASES CAUSED BY

548
00:21:22,708 --> 00:21:25,043
DENGUE 1, 2, 3, 4.

549
00:21:25,043 --> 00:21:26,511
HERE'S DENGUE 4.

550
00:21:26,511 --> 00:21:32,651
HERE IN BRAZIL, MOST OF THE

551
00:21:32,651 --> 00:21:34,853
CASES AT THAT TIME, SO NICE

552
00:21:34,853 --> 00:21:36,254
EFFICACY TO DENGUE 4, BECAUSE

553
00:21:36,254 --> 00:21:38,690
IT'S A DENGUE 4 VACCINE.

554
00:21:38,690 --> 00:21:39,157
THAT MAKES SENSE.

555
00:21:39,157 --> 00:21:40,959
IN MEXICO MOSTLY DENGUE 1 AND 2

556
00:21:40,959 --> 00:21:42,327
ARE CIRCULATING DURING THE

557
00:21:42,327 --> 00:21:46,498
TRIAL, VERY LOW EFFICACY, OKAY

558
00:21:46,498 --> 00:21:48,633
IN IRONICALLY, THE FIRST COUNTRY

559
00:21:48,633 --> 00:21:57,175
TO AUTHORIZE THIS VACCINE WAS

560
00:21:57,175 --> 00:21:57,743
MEXICO.

561
00:21:57,743 --> 00:22:00,212
DENG VAXIA WORKS REALLY WELL AS

562
00:22:00,212 --> 00:22:02,013
A FILL IN VACCINE, I DON'T WANT

563
00:22:02,013 --> 00:22:03,415
TO LEAD YOU ASTRAY AND SAY THE

564
00:22:03,415 --> 00:22:06,585
VACCINE IS NOT USEFUL BECAUSE

565
00:22:06,585 --> 00:22:07,419
THE EFFICACY AGAINST SERIOUS

566
00:22:07,419 --> 00:22:10,288
DENGUE DEC CAN BE AS HIGH AS 93%

567
00:22:10,288 --> 00:22:11,656
BUT THAT VACCINE NEEDS TO BE

568
00:22:11,656 --> 00:22:12,958
GIVEN TO SOMEBODY WHO ALREADY

569
00:22:12,958 --> 00:22:14,059
HAD DENGUE.

570
00:22:14,059 --> 00:22:16,495
IF YOU'VE HAD DENGUE THEN YOU

571
00:22:16,495 --> 00:22:18,730
CAN BE VACCINATED BECAUSE, AGAIN

572
00:22:18,730 --> 00:22:20,398
THIS IS--THIS WOULD BE WHAT WE

573
00:22:20,398 --> 00:22:22,901
WOULD CALL A SEQUENTIAL

574
00:22:22,901 --> 00:22:24,703
VACCINATION STRATEGY.

575
00:22:24,703 --> 00:22:29,007
YOU HAVE A PRIMING FROM A

576
00:22:29,007 --> 00:22:30,408
PREVIOUS EXPOSURE FROM MOTHER

577
00:22:30,408 --> 00:22:30,675
NATURE.

578
00:22:30,675 --> 00:22:32,978
MOTHER NATURE GIVES YOU THE

579
00:22:32,978 --> 00:22:34,412
FIRST DOSE, SANOFI GIVES YOU

580
00:22:34,412 --> 00:22:35,781
DOSE 2, 3, AND 4.

581
00:22:35,781 --> 00:22:37,682
OKAY IN THE BOTTOM LINE IS

582
00:22:37,682 --> 00:22:39,518
INCOMPLOAT OR PARTIAL IMMUNITY

583
00:22:39,518 --> 00:22:42,854
TO DENGUE REMAINS PROBLEMATIC.

584
00:22:42,854 --> 00:22:47,793
TAKEDA, DEVELOPED THEIR VACCINE

585
00:22:47,793 --> 00:22:50,695
DURING THEIR TRIAL THEY CALL IT

586
00:22:50,695 --> 00:22:51,263
TAK003.

587
00:22:51,263 --> 00:22:54,699
REALLY GOOD EFFICACY AGAINST

588
00:22:54,699 --> 00:22:57,202
HOSPITALIZATION, THAT'S BECAUSE

589
00:22:57,202 --> 00:22:58,270
HOSPITALIZED INDIVIDUALS ARE

590
00:22:58,270 --> 00:23:00,806
HAVING PRIMARILY A SECOND OR

591
00:23:00,806 --> 00:23:02,507
THIRD INFECTION OKAY, IF YOU

592
00:23:02,507 --> 00:23:04,242
VACCINATE THESE PEOPLE, YOU CAN

593
00:23:04,242 --> 00:23:08,847
PROTECT AGAINST A SERIOUS SECOND

594
00:23:08,847 --> 00:23:11,883
AND THIRD VACCINATION.

595
00:23:11,883 --> 00:23:15,086
BUT AGAIN THEIR IMMUNO

596
00:23:15,086 --> 00:23:15,821
GENERATEDISSITY APPEARS

597
00:23:15,821 --> 00:23:17,656
IMBALANCED, SO THEIR PUBLISHED

598
00:23:17,656 --> 00:23:18,690
DATA IN SERONAIVE INDIVIDUALS

599
00:23:18,690 --> 00:23:23,762
YOU CAN SEE THIS HUGE DOMINANCE

600
00:23:23,762 --> 00:23:26,398
FOR DENGUE 2.

601
00:23:26,398 --> 00:23:29,568
THE TAKEDA VACCINE IS

602
00:23:29,568 --> 00:23:30,402
PREDOMINANTLY A DENGUE 2

603
00:23:30,402 --> 00:23:30,635
VACCINE.

604
00:23:30,635 --> 00:23:32,304
WHEN YOU LOOK AT EFFICACY

605
00:23:32,304 --> 00:23:34,105
WHETHER IT'S 18 MONTH OR 36

606
00:23:34,105 --> 00:23:35,607
MONTH GOOD EFFICACY FOR DENGUE 1

607
00:23:35,607 --> 00:23:37,409
AND 2, THEY COULD NOT

608
00:23:37,409 --> 00:23:39,010
DEMONSTRATE EFFICACY FOR DENGUE

609
00:23:39,010 --> 00:23:40,879
4 BECAUSE THERE WERE NO CASES

610
00:23:40,879 --> 00:23:43,849
BUT THEY REPORTED NO EFFICACY TO

611
00:23:43,849 --> 00:23:44,216
DENGUE 3.

612
00:23:44,216 --> 00:23:45,750
BY 36 MONTHS THEY HAD

613
00:23:45,750 --> 00:23:47,485
ACCUMULATED A ENOUGH CASES THAT

614
00:23:47,485 --> 00:23:49,621
YOU SAW A NEGATIVE EFFICACY FOR

615
00:23:49,621 --> 00:23:54,626
DENGUE 3, A NEGATIVE EFFICACY

616
00:23:54,626 --> 00:23:55,093
FOR DENGUE 4.

617
00:23:55,093 --> 00:23:57,162
THIS WAS RECENTLY APPROVE INDEED

618
00:23:57,162 --> 00:23:59,564
SEVERAL COUNTRIES WITHOUT A

619
00:23:59,564 --> 00:24:01,967
REQUIREMENT FOR SEROPOSITIVITY

620
00:24:01,967 --> 00:24:02,500
OR REVACCINATION TESTING.

621
00:24:02,500 --> 00:24:04,302
YOU JUST WANT TO IMIF IT TO AGE

622
00:24:04,302 --> 00:24:06,371
GROUPS WHERE YOU THOUGHT MOST OF

623
00:24:06,371 --> 00:24:09,407
THE PEOPLE HAD ALREADY HAD THEIR

624
00:24:09,407 --> 00:24:10,675
FIRST INFECTION.

625
00:24:10,675 --> 00:24:14,412
THEIR APPLICATION AT THE USFDA

626
00:24:14,412 --> 00:24:15,113
HAS SUBSEQUENTLY BEEN WITHDRAWN.

627
00:24:15,113 --> 00:24:16,681
I DO NOT KNOW THE REASON FOR

628
00:24:16,681 --> 00:24:17,015
THAT.

629
00:24:17,015 --> 00:24:19,184
THERE'S LOTS OF SPECULATION

630
00:24:19,184 --> 00:24:21,286
EMPLOY OKAY, THOSE ARE THE OTHER

631
00:24:21,286 --> 00:24:21,753
VACCINES.

632
00:24:21,753 --> 00:24:28,793
NOW WHAT ABOUT THE NIH

633
00:24:28,793 --> 00:24:29,427
TETRAVALENT DENGUE VANNING SEEN.

634
00:24:29,427 --> 00:24:31,496
WE MOVED FOR HUNDREDS OF

635
00:24:31,496 --> 00:24:32,864
DIFFERENT CONSTRUCTS, VIRUS

636
00:24:32,864 --> 00:24:34,366
CONSTRUCTS, MOST OF THESE MADE

637
00:24:34,366 --> 00:24:38,403
IN THE LABORATORY BY CHRIS AND

638
00:24:38,403 --> 00:24:41,306
CATHY HANLY AND JOE BLANEY,

639
00:24:41,306 --> 00:24:42,674
HUNDREDS OF DIFFERENT

640
00:24:42,674 --> 00:24:44,976
CONSTRUCTS, SOME OF THEM

641
00:24:44,976 --> 00:24:48,313
PRECEDED THROUGH PRECLINICAL

642
00:24:48,313 --> 00:24:52,751
EVALUATION IN A LOT OF DIFFERENT

643
00:24:52,751 --> 00:24:54,286
MONKEYS, AND THEN WE CHOSE TO GO

644
00:24:54,286 --> 00:24:54,519
FORWARD.

645
00:24:54,519 --> 00:24:56,922
I PUT A GOLD STAR HERE, THIS IS

646
00:24:56,922 --> 00:24:58,657
WHAT MADE THE DIFFERENCE FOR US.

647
00:24:58,657 --> 00:25:00,258
WHY OUR VACCINE WORKS.

648
00:25:00,258 --> 00:25:02,260
BECAUSE WE WENT AND TESTED EACH

649
00:25:02,260 --> 00:25:03,428
OF THESE INDIVIDUALLY IN HUMAN

650
00:25:03,428 --> 00:25:05,597
PHASE 1 TRIALS TO MAKE SURE THEY

651
00:25:05,597 --> 00:25:10,368
WERE COMPLETELY INFECT YOWZ

652
00:25:10,368 --> 00:25:11,536
COMPLETELY REPLICATIVE, BUT THAT

653
00:25:11,536 --> 00:25:13,705
TOOK US HONESTLY ABOUT A DECADE

654
00:25:13,705 --> 00:25:16,341
AND PEOPLE KEPT ASKING JUST PUT

655
00:25:16,341 --> 00:25:17,709
THE TETRAVALENT TOGETHER BUT WE

656
00:25:17,709 --> 00:25:18,910
WEREN'T SURE WHAT TO PUT

657
00:25:18,910 --> 00:25:20,312
TOGETHER, WE WANTED TO MAKE SURE

658
00:25:20,312 --> 00:25:22,147
THIS WAS GOING TO WORK SO WE

659
00:25:22,147 --> 00:25:24,015
COULD MAKE SURE OF THIS FINAL

660
00:25:24,015 --> 00:25:24,783
FORMULATION.

661
00:25:24,783 --> 00:25:26,952
THIS FORMULATION IS A FULL

662
00:25:26,952 --> 00:25:28,853
LENGTH DENGUE 1 WITH THIS DELTA

663
00:25:28,853 --> 00:25:31,589
30 MUTATION, THIS KELTA 30

664
00:25:31,589 --> 00:25:33,692
MUTATION IS IN THE THIRD PRIME

665
00:25:33,692 --> 00:25:36,127
UTR, WE TALK OUT THIS LITTLE BIT

666
00:25:36,127 --> 00:25:39,531
OF STEM LOOP AND WHAT WE SEE IS

667
00:25:39,531 --> 00:25:41,433
INCREASED SUSCEPTIBILITY TO TYPE

668
00:25:41,433 --> 00:25:43,868
1 INTERFERONSON THAT'S HOW THE

669
00:25:43,868 --> 00:25:44,402
VIRUSES ARE ATTENUATE.

670
00:25:44,402 --> 00:25:47,906
WE DID THE SAME THING FOR DENGUE

671
00:25:47,906 --> 00:25:49,808
4, THE DELTA THIRD, WHAT WE DID

672
00:25:49,808 --> 00:25:52,677
FOR DINGHY 3 WAS CREATE A DELTA

673
00:25:52,677 --> 00:25:55,213
30, IT DIDN'T WORK SO WE NEEDED

674
00:25:55,213 --> 00:25:57,315
A DELTA 31 MUTATION SHOWN UP

675
00:25:57,315 --> 00:25:59,617
HERE AND FOR DENGUE 2, DENGUE 2

676
00:25:59,617 --> 00:26:01,586
DELTA THIRD DID NOT WORK SO WE

677
00:26:01,586 --> 00:26:08,326
MADE A CHIMERIC USING THE DENGUE

678
00:26:08,326 --> 00:26:18,770
4 AND THE PREM AND E FROM

679
00:26:20,905 --> 00:26:22,273
KENNINGY 2.

680
00:26:22,273 --> 00:26:27,112
WE CONDUCTED 31 DIFFERENT TRIALS

681
00:26:27,112 --> 00:26:28,680
FOR THIS VACCINE.

682
00:26:28,680 --> 00:26:30,515
FINALLY COMING TO A CANDIDATE

683
00:26:30,515 --> 00:26:32,584
FORMATION, WE TEST INDEED

684
00:26:32,584 --> 00:26:33,885
THAILAND AND BANGLADESH, WE

685
00:26:33,885 --> 00:26:35,820
DEMONSTRATE THAD YES IT IS A

686
00:26:35,820 --> 00:26:39,457
SINGLE DOSE VACCINE, MINIMAL

687
00:26:39,457 --> 00:26:44,229
BOOST AFTER THE SECOND DOSE IT'S

688
00:26:44,229 --> 00:26:46,398
UNIFORMLY INFECTIOUS AND

689
00:26:46,398 --> 00:26:48,800
IMMUNOGENIC IN DENGUE NAIVE

690
00:26:48,800 --> 00:26:52,203
SUBJEKS, YOU CAN FILL IT IN WITH

691
00:26:52,203 --> 00:26:54,606
THOSE USING SEROTYPES, IT'S SAFE

692
00:26:54,606 --> 00:26:57,542
IN OALTDER ADULTS, IT'S SAFE IN

693
00:26:57,542 --> 00:26:59,144
INFANTS CAN CHILDREN AS YOUNG AS

694
00:26:59,144 --> 00:27:01,146
1 YEAR, YOU GET A STRONG T-CELL

695
00:27:01,146 --> 00:27:02,647
RESPONSE, YOU CAN HAVE

696
00:27:02,647 --> 00:27:03,615
PROTECTION AFTER 30 DAYS WHICH

697
00:27:03,615 --> 00:27:07,018
IS IMPORTANT FOR THE TRAVELER,

698
00:27:07,018 --> 00:27:11,056
INDICATION, AND YOU GET--WE

699
00:27:11,056 --> 00:27:12,991
DEMONSTRATED SOLID AGAINST

700
00:27:12,991 --> 00:27:14,526
DENGUE VIRUS CHALLENGE, 2 AND 3.

701
00:27:14,526 --> 00:27:15,493
VERY QUICKLY HERE'S THE DESIGN

702
00:27:15,493 --> 00:27:25,637
OF THE STUDY WE DID IN BANGKOK,

703
00:27:25,637 --> 00:27:28,440
HD ESCALATION STUDY, LOOKING AT

704
00:27:28,440 --> 00:27:29,941
SAFETY, IMMUNO GENERATEDISSITY,

705
00:27:29,941 --> 00:27:32,243
VIREMIA, AND DETERMINING THE

706
00:27:32,243 --> 00:27:33,411
EFFECT OF PREEXISTING ANTIBODY.

707
00:27:33,411 --> 00:27:35,046
VERY QUICKLY, I THINK I SKIP

708
00:27:35,046 --> 00:27:37,415
DOWN HERE REALLY QUICK BECAUSE I

709
00:27:37,415 --> 00:27:38,349
WANT TO SHOW YOU.

710
00:27:38,349 --> 00:27:39,984
THIS IS WHAT INDIVIDUALS IN

711
00:27:39,984 --> 00:27:41,586
BANGKOK LOOK LIKE THAT WERE

712
00:27:41,586 --> 00:27:44,456
ENROLLED IN THE STUDY.

713
00:27:44,456 --> 00:27:46,091
BEFORE VACCINATION, SO PREVAXIA,

714
00:27:46,091 --> 00:27:49,427
73% OF THE ADULTS HAD A

715
00:27:49,427 --> 00:27:50,595
NEUTRALIZING ANTIBODY TITER

716
00:27:50,595 --> 00:27:52,363
AGAINST ALL 4 SERO TYPES, MOST

717
00:27:52,363 --> 00:27:54,866
OF THEM, ALMOST ALL OF THEM HAD

718
00:27:54,866 --> 00:27:59,270
ANTIBODY AGAINST AT LEAST 1 OR 2

719
00:27:59,270 --> 00:28:00,171
SEROTYPES OF DENGUE.

720
00:28:00,171 --> 00:28:02,507
THIS IS WHAT ADULTS LOOK LIKE IN

721
00:28:02,507 --> 00:28:02,841
BANGKOK.

722
00:28:02,841 --> 00:28:05,143
YOUNG KIDS, YOU KNOW ONLY 4% OF

723
00:28:05,143 --> 00:28:07,679
THEM HAD A REALLY COMPLETE

724
00:28:07,679 --> 00:28:09,547
IMMUNE RESPONSE TO DENGUE.

725
00:28:09,547 --> 00:28:12,250
SO THIS IS--THIS IS NATURAL

726
00:28:12,250 --> 00:28:14,152
SEQUENTIAL IMMUNITY AT WORK HERE

727
00:28:14,152 --> 00:28:16,821
IN THE ADULTS.

728
00:28:16,821 --> 00:28:20,291
THIS IS WHAT WE SAW AFTER

729
00:28:20,291 --> 00:28:20,658
VACCINATION.

730
00:28:20,658 --> 00:28:22,961
EVERYBODY MOVES CLOSER TO THAT

731
00:28:22,961 --> 00:28:25,897
END POINT INCLUDING THE YOUNG

732
00:28:25,897 --> 00:28:26,631
CHILDREN, OKAY, REMEMBER, I

733
00:28:26,631 --> 00:28:29,067
ASKED YOU AT THE VERY BEGINNING,

734
00:28:29,067 --> 00:28:31,136
CAN THIS TYPE OF NATURAL

735
00:28:31,136 --> 00:28:33,171
IMMUNITY BE INDUCED IN YOUNG

736
00:28:33,171 --> 00:28:33,738
CHILDREN?

737
00:28:33,738 --> 00:28:36,341
CAN WE SAFELY INDUCE THIS IPT

738
00:28:36,341 --> 00:28:37,142
GREATERUNITY IN CHILDREN?

739
00:28:37,142 --> 00:28:40,478
AND MY ANSWER WOULD BE YES.

740
00:28:40,478 --> 00:28:41,913
THESE CHILDREN'S IMMUNE PROFILE,

741
00:28:41,913 --> 00:28:43,414
THAT LOOKS VERY SIMILAR TO WHAT

742
00:28:43,414 --> 00:28:48,319
YOU SEE AFTER NATURAL INFECTION

743
00:28:48,319 --> 00:28:48,953
IN ADULTS.

744
00:28:48,953 --> 00:28:50,822
WE HAVE DEVELOPED A HUMAN

745
00:28:50,822 --> 00:28:51,556
CONTROLLED INFECTION MODEL

746
00:28:51,556 --> 00:28:53,491
DURING THIS PROCESS, SO A MODEL

747
00:28:53,491 --> 00:28:56,194
FOR DENGUE 2 AND 3.

748
00:28:56,194 --> 00:28:57,829
WE ADMINISTERED THIS VIRUS, NOT

749
00:28:57,829 --> 00:29:00,265
A VACCINE, IT'S A VIRUS, TO

750
00:29:00,265 --> 00:29:02,300
ADULTS HERE IN THE U.S., A

751
00:29:02,300 --> 00:29:05,270
HUNDRED% OF THEM HAVE A VIREMIA,

752
00:29:05,270 --> 00:29:08,072
WITH A PEAK TITER SOMEWHERE

753
00:29:08,072 --> 00:29:12,877
ABOVE 2 LOGS FOR DENGUE 2, LOWER

754
00:29:12,877 --> 00:29:13,444
FOR DENGUE 3.

755
00:29:13,444 --> 00:29:15,180
MOST OF THESE INDIVIDUALS HAVE A

756
00:29:15,180 --> 00:29:17,515
RASH, THIS IS WHAT THE TYPICAL

757
00:29:17,515 --> 00:29:19,884
RASH LOOKS LIKE, SO THIS IS THE

758
00:29:19,884 --> 00:29:23,188
RASH FROM OUR DENGUE 2 CONTROL

759
00:29:23,188 --> 00:29:24,055
INFECTION MODEL, OUR DENGUE 3,

760
00:29:24,055 --> 00:29:29,194
THIS IS THE CROSSED LEGS OF A

761
00:29:29,194 --> 00:29:30,795
NATURAL INFECTED PERSON AND THIS

762
00:29:30,795 --> 00:29:34,532
IS ON THE CHEST OF THIS

763
00:29:34,532 --> 00:29:35,767
VOLUNTEER, THESE LITTLE MACULES,

764
00:29:35,767 --> 00:29:37,735
HA'S WHAT WE SEE WITH THE DENGUE

765
00:29:37,735 --> 00:29:38,069
VACCINE.

766
00:29:38,069 --> 00:29:41,072
SO THE DENGUE VACCINE IS VERY

767
00:29:41,072 --> 00:29:43,575
DIFFERENT RASH FROM WHAT WE SEE

768
00:29:43,575 --> 00:29:46,611
IN NATURAL INFECTION OR HUMAN

769
00:29:46,611 --> 00:29:47,212
CONTROL MODEL.

770
00:29:47,212 --> 00:29:49,480
SO WE WILL SET UP A STUDY WHERE

771
00:29:49,480 --> 00:29:51,382
WE VACCINATE OR GIVE PLACEBOS TO

772
00:29:51,382 --> 00:29:53,318
2 GROUPS OF INDIVIDUALS, WE WILL

773
00:29:53,318 --> 00:29:57,121
COME BACK WITH A THOUSAND FFU OF

774
00:29:57,121 --> 00:30:01,359
DENGUE  VIRUS, WE WILL LOOK AT

775
00:30:01,359 --> 00:30:03,127
THIS FOR PROTECTION AGAINST RASH

776
00:30:03,127 --> 00:30:03,695
AND THE VIRUS.

777
00:30:03,695 --> 00:30:07,165
THIS IS WHAT WE SEE.

778
00:30:07,165 --> 00:30:09,601
IN OUR PLACEBOS A HUNDRED

779
00:30:09,601 --> 00:30:10,902
PERCENT INFECTION, A HUNDRED%

780
00:30:10,902 --> 00:30:11,703
RASH.

781
00:30:11,703 --> 00:30:13,905
IN SACK SINEES, NO VIREMIA AND

782
00:30:13,905 --> 00:30:16,507
NO RASH, SAME FOR DENGUE 3, NO

783
00:30:16,507 --> 00:30:18,910
VIREMIA, NO RASH, WE ARE A

784
00:30:18,910 --> 00:30:20,278
HUNDRED% PROTECTION IMON

785
00:30:20,278 --> 00:30:23,448
STRAIGHTED IN OUR CONTROLLED

786
00:30:23,448 --> 00:30:24,349
HUMAN INFECTION MODEL.

787
00:30:24,349 --> 00:30:25,817
OKAY, WE HAVE A VACCINE, WE

788
00:30:25,817 --> 00:30:28,653
THINK IT'S GOING TO WORK.

789
00:30:28,653 --> 00:30:29,954
WHAT ARE WE GOING TO DO WITH

790
00:30:29,954 --> 00:30:33,191
THIS IN WE TURN TO TECHNOLOGY

791
00:30:33,191 --> 00:30:35,059
TRANSFER AND WE HAVE LICENSED

792
00:30:35,059 --> 00:30:36,828
THIS TECHNOLOGY WHICH INCLUES

793
00:30:36,828 --> 00:30:38,396
THE PATENT RISE, BIOLOGICAL

794
00:30:38,396 --> 00:30:39,764
MATERIALS, METHODS AND

795
00:30:39,764 --> 00:30:41,466
PROCEDURES, ALL OF OUR PHASE 1

796
00:30:41,466 --> 00:30:44,135
AND 2 DATA TO SUPPORT THE

797
00:30:44,135 --> 00:30:46,304
REGULATORY FILINGS, AND IT ALSO

798
00:30:46,304 --> 00:30:48,706
INVOLVES A LOT OF HAND HOLDING

799
00:30:48,706 --> 00:30:49,040
FROM OUR END.

800
00:30:49,040 --> 00:30:51,376
YOU CAN'T JUST LICENSE AND WALK

801
00:30:51,376 --> 00:30:51,576
AWAY.

802
00:30:51,576 --> 00:30:54,112
THAT GENERALLY DOESN'T WORK.

803
00:30:54,112 --> 00:30:55,613
WE LICENSE THIS COMPANY FOR USE

804
00:30:55,613 --> 00:31:03,454
IN THE U.S., EUROPE AND CHINA,

805
00:31:03,454 --> 00:31:05,990
TO THE BUTANTAN IN BRAZIL, WE

806
00:31:05,990 --> 00:31:08,993
ARE NOW WITH 4 IN INDIA, AND

807
00:31:08,993 --> 00:31:16,801
WE'RE WITH DR. REDDY'S

808
00:31:16,801 --> 00:31:18,670
PHARMACEUTICALS, AND WE'VE ALSO

809
00:31:18,670 --> 00:31:20,271
WORKED HERE ON THE GOVERNMENT'S

810
00:31:20,271 --> 00:31:22,573
REQUEST TO WORK ON THE

811
00:31:22,573 --> 00:31:25,310
DEVASTATING DENGUE SEASON

812
00:31:25,310 --> 00:31:30,682
THEY'VE HAD WITH MEDIgE N, AND

813
00:31:30,682 --> 00:31:32,950
VABIO TECH, AND HERE'S THE FIRST

814
00:31:32,950 --> 00:31:35,687
PHASE 3 STUDY   PERFORMED BY THE

815
00:31:35,687 --> 00:31:37,689
FIRST INSTIEWS BUTAN TAN, THIS

816
00:31:37,689 --> 00:31:40,058
IS THE NIH VACCINE PRODUCED IN

817
00:31:40,058 --> 00:31:43,027
THEIR HANDS PRODUCED IN THEIR

818
00:31:43,027 --> 00:31:45,129
FACILITIES, IT'S BEEN PUBLISHED

819
00:31:45,129 --> 00:31:47,865
IN 2 DIFFERENT JOURNALS.

820
00:31:47,865 --> 00:31:49,167
THIS STUDY WAS 16,000

821
00:31:49,167 --> 00:31:51,903
INDIVIDUALS IN 16 CLINICAL SITES

822
00:31:51,903 --> 00:31:52,370
ACROSS BRAZIL.

823
00:31:52,370 --> 00:31:56,574
THE STUDY WAS CONDUCTED WITH

824
00:31:56,574 --> 00:31:57,041
IMPECCABLE PRECISION.

825
00:31:57,041 --> 00:32:01,846
IF YOU LOOK AT THIS, 10,259

826
00:32:01,846 --> 00:32:02,513
RECEIVED VACCINATION.

827
00:32:02,513 --> 00:32:08,319
AT THE END OF THIS ANALYSIS AT

828
00:32:08,319 --> 00:32:10,621
3.7 YEARS, 10,215 OF THEM WERE

829
00:32:10,621 --> 00:32:12,256
STILL IN THE   PERPROTOCOL

830
00:32:12,256 --> 00:32:14,759
EFFICACY POPULATION, THIS IS

831
00:32:14,759 --> 00:32:16,928
REMARKABLE RETENTION FOR A PHASE

832
00:32:16,928 --> 00:32:17,562
3 STUDY.

833
00:32:17,562 --> 00:32:19,831
SO KUDOS TO THEM.

834
00:32:19,831 --> 00:32:22,767
HD ESCALATION, THIS WAS THE

835
00:32:22,767 --> 00:32:33,111
FIRST VACCINATION ON

836
00:32:47,492 --> 00:32:48,593
FEBRUARY 2016--WHAT WE DID, WHAT

837
00:32:48,593 --> 00:32:50,161
THEY THEN DID IS A 2 YEAR

838
00:32:50,161 --> 00:32:53,564
ANALYSIS THAT WAS CARRIED OUT ON

839
00:32:53,564 --> 00:32:54,632
JULY 13th 2021, EVERYBODY IN

840
00:32:54,632 --> 00:32:57,902
THAT STUDY HAD COMPLETED 2 YEARS

841
00:32:57,902 --> 00:33:00,872
OF A VACCINATION ON THAT CUT OFF

842
00:33:00,872 --> 00:33:01,072
DATE.

843
00:33:01,072 --> 00:33:06,177
THEY ALSO DID AN ANALYSIS WHERE

844
00:33:06,177 --> 00:33:08,813
AT THAT CUT OFF DATE THEY LOOKED

845
00:33:08,813 --> 00:33:10,448
ADDED ALL THE EFFICACY

846
00:33:10,448 --> 00:33:12,283
REGARDLESS OF TIME SINCE

847
00:33:12,283 --> 00:33:13,951
VACCINATION, A MEAN OF 3.7

848
00:33:13,951 --> 00:33:14,185
YEARS.

849
00:33:14,185 --> 00:33:16,020
SOME OF THESE INDIVIDUALS HAD

850
00:33:16,020 --> 00:33:19,157
ALREADY REACHED OUR 5 YEAR

851
00:33:19,157 --> 00:33:19,357
POINT.

852
00:33:19,357 --> 00:33:21,592
AND THEN THERE WILL BE A 5 YEAR

853
00:33:21,592 --> 00:33:23,094
ANALYSIS WHICH IS ONGOING

854
00:33:23,094 --> 00:33:24,595
BECAUSE THE STUDY COMPLETED ON

855
00:33:24,595 --> 00:33:28,065
JULY 13th OF THIS YEAR, 0 TO 6

856
00:33:28,065 --> 00:33:29,901
MONTHS POST VACCINATION FOR

857
00:33:29,901 --> 00:33:30,401
EVERYBODY.

858
00:33:30,401 --> 00:33:33,404
AND IN BRAZIL, THE INCIDENCE OF

859
00:33:33,404 --> 00:33:35,373
DENGUE SHOWN IN THE BLUE LINE

860
00:33:35,373 --> 00:33:38,676
VARIES FROM YEAR TO YEAR, BUT

861
00:33:38,676 --> 00:33:40,611
DURING THIS TRIAL, WHAT DIDN'T

862
00:33:40,611 --> 00:33:42,747
VARY WAS THE LACK OF CIRCULATION

863
00:33:42,747 --> 00:33:45,450
OF DENGUE 3 AND 4 AND YOU CAN

864
00:33:45,450 --> 00:33:47,852
SEE DOWN HERE WHAT% OF THE CASES

865
00:33:47,852 --> 00:33:51,622
WERE CAUSED BY DENGUE 3 AND 4.

866
00:33:51,622 --> 00:33:53,691
THEY DID HAVE AN OUTBREAK OF

867
00:33:53,691 --> 00:33:58,196
DENGUE 3 BEGINNING IN 2023 INTO

868
00:33:58,196 --> 00:33:58,429
2024.

869
00:33:58,429 --> 00:33:59,864
WE WERE HOPING TO HAVE SOME OF

870
00:33:59,864 --> 00:34:03,935
THOSE CASES IN THE TRIAL BY THE

871
00:34:03,935 --> 00:34:08,105
CUT OFF POINT, JULY OF THIS

872
00:34:08,105 --> 00:34:08,706
YEAR.

873
00:34:08,706 --> 00:34:10,441
THEY HAD CAPTURED 0 CASES, STILL

874
00:34:10,441 --> 00:34:11,676
0 CASES OF DENGUE 3, MOSTLY

875
00:34:11,676 --> 00:34:17,048
BECAUSE IT WAS IN AREAS THAT

876
00:34:17,048 --> 00:34:20,017
WERE NO LONGER HAD VACCINEES

877
00:34:20,017 --> 00:34:21,419
BEING MONITORS AND ALSO THERE

878
00:34:21,419 --> 00:34:23,321
WAS REALLY ONLY ABOUT A THOUSAND

879
00:34:23,321 --> 00:34:26,624
INDIVIDUALS LEFT IN THE TRIAL AT

880
00:34:26,624 --> 00:34:27,391
THAT POINT.

881
00:34:27,391 --> 00:34:31,696
LOOKING AT THE 2 YEAR EFFICACY

882
00:34:31,696 --> 00:34:34,866
DATA, OVERALL 80% EFFICACY AFTER

883
00:34:34,866 --> 00:34:38,202
2 YEARS, SPHEVENT% FOR DENGUE 2,

884
00:34:38,202 --> 00:34:40,571
90% FOR DENGUE 1, AGAIN NO

885
00:34:40,571 --> 00:34:41,839
CIRCULATION OF DENGUE 3 AND 4 SO

886
00:34:41,839 --> 00:34:45,510
WE CAN'T COMMENT ON THE EFFICACY

887
00:34:45,510 --> 00:34:46,143
AT THAT POINT.

888
00:34:46,143 --> 00:34:48,246
AT THE CUT OFF WHICH WAS A MEAN

889
00:34:48,246 --> 00:34:52,617
OF ALMOST 4 YEARS, WE'RE STILL

890
00:34:52,617 --> 00:34:53,150
67% OVERALL EFFICACY.

891
00:34:53,150 --> 00:34:56,287
YOU CAN SEE THE EFFICACY FOR

892
00:34:56,287 --> 00:35:01,425
DENGUE 1 AND 2.

893
00:35:01,425 --> 00:35:03,227
HERE'S THE INCIDENCE CURVES

894
00:35:03,227 --> 00:35:05,830
AFTER 3.7 YEARS.

895
00:35:05,830 --> 00:35:09,333
HERE'S PLACEBOS, HERE ARE

896
00:35:09,333 --> 00:35:10,635
VACCINEES, AGAIN 67% EFFICACY.

897
00:35:10,635 --> 00:35:13,938
YOU CAN SEE THIS LITTLE INCREASE

898
00:35:13,938 --> 00:35:17,341
THAT OCCURRED IN 2023, STILL IN

899
00:35:17,341 --> 00:35:20,278
PLACEBOS IT'S A RATHER FLAT

900
00:35:20,278 --> 00:35:23,014
INCIDENCE LINE.

901
00:35:23,014 --> 00:35:25,116
HERE'S THE--ALL OF THE EFFICACY

902
00:35:25,116 --> 00:35:27,218
STRATIFIED BY AGE AND WHETHER OR

903
00:35:27,218 --> 00:35:30,054
NOT YOU'RE EXPOSED TO DENGUE OR

904
00:35:30,054 --> 00:35:31,656
NOT EXPOSED TO DENGUE.

905
00:35:31,656 --> 00:35:34,258
YOU CAN SEE IN RED ARE THE

906
00:35:34,258 --> 00:35:36,394
VALUES FOR THE DIFFERENT AGE

907
00:35:36,394 --> 00:35:39,163
GROUPS, FOR THE GROUP REGARDLESS

908
00:35:39,163 --> 00:35:43,067
OF SEROTYPE, YOU CAN SEE MY

909
00:35:43,067 --> 00:35:46,938
FAVORITE HERE IS THIS 80% VALUE.

910
00:35:46,938 --> 00:35:49,340
THIS IS 2-6 YEAR-OLDS,

911
00:35:49,340 --> 00:35:50,641
REGARDLESS OF WHETHER THEY'RE

912
00:35:50,641 --> 00:35:54,512
POSITIVE OR NEGATIVE, WE HAVE

913
00:35:54,512 --> 00:35:57,682
EFFICACY OF 80% IN THIS YOUNGEST

914
00:35:57,682 --> 00:35:58,082
GROUP.

915
00:35:58,082 --> 00:36:02,119
WHAT ABOUT SEVERE DENGUE.

916
00:36:02,119 --> 00:36:04,121
EIGHTY-NINE% EFFICACY AFTER 3.7

917
00:36:04,121 --> 00:36:08,559
YEARS. 

918
00:36:08,559 --> 00:36:12,330
IF WE LOOK AT THE 2 YEAR DATA,

919
00:36:12,330 --> 00:36:15,533
IT WAS 88%, OKAY.

920
00:36:15,533 --> 00:36:16,834
TWO YEARS, ALMOST 4 YEARS, WE

921
00:36:16,834 --> 00:36:19,103
HAVE THE SAME EFFICACY FOR

922
00:36:19,103 --> 00:36:19,870
SERIOUS DENGUE.

923
00:36:19,870 --> 00:36:24,442
IF YOU COMPARE THIS TO TAKEDA'S

924
00:36:24,442 --> 00:36:26,644
PUBLISHED 3 YEARS, 84%, IF WE

925
00:36:26,644 --> 00:36:29,413
STRATIFY IT BY DENGUE WOKNOW AND

926
00:36:29,413 --> 00:36:31,148
2, 93%, 85%, THIS VACCINE CAN

927
00:36:31,148 --> 00:36:33,884
HAVE A GREAT EFFECT ON

928
00:36:33,884 --> 00:36:36,787
HOSPITALIZATION AND SEVERE

929
00:36:36,787 --> 00:36:37,588
DISEASE.

930
00:36:37,588 --> 00:36:39,223
THIS IS THE ADVERSE EVENTS FROM

931
00:36:39,223 --> 00:36:39,824
THE TRIAL.

932
00:36:39,824 --> 00:36:42,693
AS I MENTIONED AND SHOWED YOU

933
00:36:42,693 --> 00:36:45,062
THE PICTURE, THE MOST

934
00:36:45,062 --> 00:36:47,565
PREDOMINANT ADVERSE EVENT IS THE

935
00:36:47,565 --> 00:36:50,067
SKIN RASH, IT'S GENERALLY NOT

936
00:36:50,067 --> 00:36:52,036
RECOGNIZED BY THE VACCINEE, IN

937
00:36:52,036 --> 00:36:53,404
FACT IN CLINICAL TRIALS WE WOULD

938
00:36:53,404 --> 00:36:55,439
ASK DO YOU HAVE A RASH?

939
00:36:55,439 --> 00:36:57,141
AND THEY WOULD SAY NO.

940
00:36:57,141 --> 00:36:59,777
THEN THEY HAD A PHYSICAL EXAM

941
00:36:59,777 --> 00:37:02,213
WHERE THEIR SHIRT WAS REMOVED

942
00:37:02,213 --> 00:37:04,949
AND DR. ANADURB AN, EAGILAE DURB

943
00:37:04,949 --> 00:37:06,017
AN YOU WOULD POINT OUT YOU

944
00:37:06,017 --> 00:37:08,419
ACTUALLY DO HAVE A RASH, IT

945
00:37:08,419 --> 00:37:09,954
USUALLY OCCURRED ON THE CHEST OR

946
00:37:09,954 --> 00:37:11,656
INSIDE OF THE ARMS.

947
00:37:11,656 --> 00:37:14,258
SOMETIMES IT IS A LITTLE BIT

948
00:37:14,258 --> 00:37:18,596
ITCHY BUT IT'S VERY SHORT LIVED.

949
00:37:18,596 --> 00:37:21,732
FOURTH APPEARANCE WE CAN LOOK AT

950
00:37:21,732 --> 00:37:23,200
BENCHMARKING AGAINST OTHER

951
00:37:23,200 --> 00:37:24,735
DENGUE VACCINES SO I'M ONLY

952
00:37:24,735 --> 00:37:28,539
SHOWING YOU PUBLISHED DATA FROM

953
00:37:28,539 --> 00:37:34,979
THESE OTHER 2 VACCINES AND FROM

954
00:37:34,979 --> 00:37:36,313
THE BUTANTAN VACCINE.

955
00:37:36,313 --> 00:37:42,153
SO HERE'S THE 2 YEAR FOLLOW UP

956
00:37:42,153 --> 00:37:45,623
FOR SANOFI, TAKEDA, OR BUTANTAN.

957
00:37:45,623 --> 00:37:46,290
AFTER THE INJECTIONS EMPLOY IF

958
00:37:46,290 --> 00:37:48,492
YOU LOOK AT THE 3 YEAR FOLLOW UP

959
00:37:48,492 --> 00:37:50,127
DATA THERE'S NOTHING REALLY IN

960
00:37:50,127 --> 00:37:54,432
THE LITERATURE FOR SANOFI, 62%

961
00:37:54,432 --> 00:37:58,102
FOR TAKEDA, THE BUTANTANAFTER A

962
00:37:58,102 --> 00:38:01,706
SINGLE DOSE IS STILL AT 67%. 

963
00:38:01,706 --> 00:38:06,711
IF YOU LOOK AT WHAT STRATIFY IT

964
00:38:06,711 --> 00:38:09,046
BY SEROEXPOSED, 74% OF

965
00:38:09,046 --> 00:38:11,749
SERONAIVES WITH THE

966
00:38:11,749 --> 00:38:12,683
BUTANTAN VACCINE ARE PROTECTED.

967
00:38:12,683 --> 00:38:14,151
THAT IS PRETTY MUCH EQUIVALENT

968
00:38:14,151 --> 00:38:17,955
TO WHAT YOU SEE IN SEROEXPOSED

969
00:38:17,955 --> 00:38:21,792
OR SERONAIVE OR SANOFI OR

970
00:38:21,792 --> 00:38:22,026
TAKEDA.

971
00:38:22,026 --> 00:38:26,197
WHEN YOU LOOK AT AGE, AGAIN,

972
00:38:26,197 --> 00:38:29,233
THIS IS 80% NUMBER.

973
00:38:29,233 --> 00:38:31,469
80 PERCENT PROTECTION FOR AGE

974
00:38:31,469 --> 00:38:35,306
2-6 YEAR-OLDS. 

975
00:38:35,306 --> 00:38:45,816
THIS GROUP HAD 84% SERONIGH

976
00:38:45,816 --> 00:38:46,016
EVITY.

977
00:38:46,016 --> 00:38:50,721
EIGHTY% IS BET ARE GROUP THE

978
00:38:50,721 --> 00:38:56,594
GROUP OF TAKEDA, OR SANOFI, AND

979
00:38:56,594 --> 00:38:58,829
IF YOU LOOK AT 6-7 YEARS IT'S

980
00:38:58,829 --> 00:38:59,163
75%.

981
00:38:59,163 --> 00:39:00,698
WHAT ABOUT THE DIFFERENT

982
00:39:00,698 --> 00:39:02,099
SEROTYPES IN WE DON'T KNOW WHAT

983
00:39:02,099 --> 00:39:03,400
THE EFFICACY WILL BE FOR DENGUE

984
00:39:03,400 --> 00:39:05,035
3 AND 4, BUT WE HAVE SOME

985
00:39:05,035 --> 00:39:07,838
INDICATIONS AND THIS GOES BACK

986
00:39:07,838 --> 00:39:12,977
TO MY ORIGINAL IDEA THAT MAYBE

987
00:39:12,977 --> 00:39:17,381
YOU CAN LOOK FOR A CORLATTIVE

988
00:39:17,381 --> 00:39:20,384
PROTECTION BY HOW MUCH VACCINE

989
00:39:20,384 --> 00:39:22,820
VIREMIA YOU'RE  SEEING.

990
00:39:22,820 --> 00:39:24,822
SEE HERE'S THE VACCINE VIREMIA

991
00:39:24,822 --> 00:39:26,624
PUBLISHED DAILY BASIS THEA AFTER

992
00:39:26,624 --> 00:39:29,660
A SINGLE DOSE IN FLAVI-NAIVE

993
00:39:29,660 --> 00:39:29,927
SUBJECTS.

994
00:39:29,927 --> 00:39:32,830
SO THIS A VERY RELEVANT

995
00:39:32,830 --> 00:39:33,297
COMPARISON.

996
00:39:33,297 --> 00:39:36,433
ALL SERONAIVES, ALL SINGLE DOSE.

997
00:39:36,433 --> 00:39:39,236
SANOFI VACCINE IS PRINCIPALLY A

998
00:39:39,236 --> 00:39:39,870
DENGUE 4 VACCINE.

999
00:39:39,870 --> 00:39:42,106
THIS IS WHERE YOU SEE MOST OF

1000
00:39:42,106 --> 00:39:46,143
THE RTPC R VIREMIA FOR THAT

1001
00:39:46,143 --> 00:39:46,477
VACCINE.

1002
00:39:46,477 --> 00:39:48,546
FOR TAKEDA, MOST OF IT IS FOUND

1003
00:39:48,546 --> 00:39:50,447
AS DENGUE 2, ALL OF IT IS FOUND

1004
00:39:50,447 --> 00:39:50,881
IN DENGUE 2.

1005
00:39:50,881 --> 00:39:53,450
I WILL GIVE YOU A CAVEAT, THIS

1006
00:39:53,450 --> 00:39:54,919
IS A SLIGHTLY DEFINITE

1007
00:39:54,919 --> 00:39:56,754
FORMULATION THAN THEY USE IN THE

1008
00:39:56,754 --> 00:39:57,955
PHASE 3 TRIAL, THEY HAVEN'T

1009
00:39:57,955 --> 00:39:59,557
PUBLISHED WITH THE PHASE 3

1010
00:39:59,557 --> 00:40:01,225
TRIAL, BUT THEY MADE ADJUSTMENTS

1011
00:40:01,225 --> 00:40:02,793
WITH THE SEROTYPES BUT

1012
00:40:02,793 --> 00:40:03,594
PRINCIPALLY IT'S DENGUE 2, THIS

1013
00:40:03,594 --> 00:40:06,997
IS WHAT YOU SEE FOR DENGUE 4.

1014
00:40:06,997 --> 00:40:08,799
WE HAVE REPLICATION OF ALL 4

1015
00:40:08,799 --> 00:40:09,066
SEROTYPES.

1016
00:40:09,066 --> 00:40:10,901
IF YOU LOOK AT THIS LEVEL OF

1017
00:40:10,901 --> 00:40:12,069
REPLICATION, I WOULD PREDICT

1018
00:40:12,069 --> 00:40:14,939
THAT THE DENGUE 3 AND 4 EFFICACY

1019
00:40:14,939 --> 00:40:16,473
IS GOING TO BE COMPARABLE OR

1020
00:40:16,473 --> 00:40:17,875
EVEN BETTER THAN WHAT WE OBSERVE

1021
00:40:17,875 --> 00:40:23,380
FOR DENGUE 1 AND 2.

1022
00:40:23,380 --> 00:40:28,185
IS IT REALLY A 1 DOSE VACCINE?

1023
00:40:28,185 --> 00:40:29,587
MERK WAS SKEPTICAL, THEY DIDN'T

1024
00:40:29,587 --> 00:40:31,121
BELIEVE US, THEY RAN THEIR OWN

1025
00:40:31,121 --> 00:40:31,355
TRIAL.

1026
00:40:31,355 --> 00:40:32,489
HERE'S THE DATA WHEN YOU LOOK AT

1027
00:40:32,489 --> 00:40:34,258
PERCENT OF SUBSCRECTS WITH

1028
00:40:34,258 --> 00:40:37,127
VIREMIA AFTER 1 DOSE, WE SEE

1029
00:40:37,127 --> 00:40:39,463
VIREMIA ACROSS ALL 4 SEROTYPES,

1030
00:40:39,463 --> 00:40:43,267
ANY SEROTYPE IT WAS 97% AFTER

1031
00:40:43,267 --> 00:40:46,170
DOSE 2 NO DETECTABLE VIREMIA.

1032
00:40:46,170 --> 00:40:46,370
OKAY?

1033
00:40:46,370 --> 00:40:49,673
SO IF YOU ARE LOOKING AT DOSE 2

1034
00:40:49,673 --> 00:40:54,545
AS SOME KIND OF CHALLENGE YOU

1035
00:40:54,545 --> 00:40:57,815
ARE STERILELY IMMUNE TO A BOOST

1036
00:40:57,815 --> 00:40:58,549
FROM FROM THAT SECOND DOSE AND

1037
00:40:58,549 --> 00:41:03,954
OF COURSE IN THE PLACEBOS WE SAW

1038
00:41:03,954 --> 00:41:04,555
NOTHING.

1039
00:41:04,555 --> 00:41:06,423
NOW THAT'S LOOKING AT VACCINE

1040
00:41:06,423 --> 00:41:08,692
VIREMIA, WHAT ABOUT LOOKING AT

1041
00:41:08,692 --> 00:41:09,193
NEUTRALIZING ANTIBODIES.

1042
00:41:09,193 --> 00:41:13,397
I HAVE TO TELL YOU THAT WHEN WE

1043
00:41:13,397 --> 00:41:15,799
LOOK AT NEUTRALIZING ANTIBODIES,

1044
00:41:15,799 --> 00:41:17,001
WE NEED TO DISCRIMINATE BETWEEN

1045
00:41:17,001 --> 00:41:18,669
THOSE THAT ARE HOMOTYPIC, TO THE

1046
00:41:18,669 --> 00:41:21,305
VIRUS THAT WAS INFECTING AND

1047
00:41:21,305 --> 00:41:25,376
THOSE THAT ARE HETEROTYPIC OR

1048
00:41:25,376 --> 00:41:27,144
CROSS REACTIVE SO AARON

1049
00:41:27,144 --> 00:41:29,246
[INDISCERNIBLE] AT UNC HAS THIS

1050
00:41:29,246 --> 00:41:30,614
RATHER COMPLICATED ASSAY WHERE

1051
00:41:30,614 --> 00:41:33,651
WE CAN DEPLETE OUT CROSS

1052
00:41:33,651 --> 00:41:34,318
REACTIVE NEUTRALIZING

1053
00:41:34,318 --> 00:41:34,618
ANTIBODIES.

1054
00:41:34,618 --> 00:41:36,553
SO YOU'RE LEFT WITH JUST

1055
00:41:36,553 --> 00:41:39,323
HOMOTYPIC ANTIBODIES, IF YOU DO

1056
00:41:39,323 --> 00:41:42,927
THAT, MOST OF THE HOMOTYPIC

1057
00:41:42,927 --> 00:41:43,994
ANTIBODIES FOR SANOFI ARE DENGUE

1058
00:41:43,994 --> 00:41:47,665
4 AS YOU WOULD PREDICT, MOST OF

1059
00:41:47,665 --> 00:41:53,404
THEM FOR TAKEDA ARE DENGUE 2,

1060
00:41:53,404 --> 00:41:55,839
YOU SEE HOMOTYPIC NONCROSS

1061
00:41:55,839 --> 00:41:57,508
REACTIVE NEUTRALIZING ANTIBODIES

1062
00:41:57,508 --> 00:42:00,711
TO ALL 4 SEROTYPES FOR THE NIH

1063
00:42:00,711 --> 00:42:01,578
VACCINE.

1064
00:42:01,578 --> 00:42:04,949
SO WE HYPOTHESIZE THAT TYPE

1065
00:42:04,949 --> 00:42:05,749
SPECIFIC HOMOTYPIC NEUTRALIZING

1066
00:42:05,749 --> 00:42:07,284
ANTIBODIES MAY BE A CORRELATIVE

1067
00:42:07,284 --> 00:42:07,618
PROTECTION.

1068
00:42:07,618 --> 00:42:09,253
WE WILL NEVER BE ABLE TO USE

1069
00:42:09,253 --> 00:42:10,888
THIS ASSAY GOING FORWARD BECAUSE

1070
00:42:10,888 --> 00:42:12,022
OF THE COMPLEXITY BUT WE'RE

1071
00:42:12,022 --> 00:42:13,891
REALLY TRYING TO WORK ON

1072
00:42:13,891 --> 00:42:16,694
DIFFERENT ASSAYS THAT WE COULD

1073
00:42:16,694 --> 00:42:25,202
USE TO LOOK AT THESE HOMOTYPIC

1074
00:42:25,202 --> 00:42:26,403
NEUTRALIZING ANTIBODY RESPONSES.

1075
00:42:26,403 --> 00:42:30,074
A PHASE 33 TRIAL FOR DENGUE ALL,

1076
00:42:30,074 --> 00:42:32,943
THAT'S THE NAME OF THE VACCINE

1077
00:42:32,943 --> 00:42:35,145
PRODUCED BY BIOTECH IN INDIA, IT

1078
00:42:35,145 --> 00:42:36,580
BEGAN JUST EARLIER THIS MONTH.

1079
00:42:36,580 --> 00:42:39,283
IT'S A MULTICENTER RANDOMIZED

1080
00:42:39,283 --> 00:42:39,850
DOUBLE BLIND PLACEBO CONTROL

1081
00:42:39,850 --> 00:42:42,319
STUDY TO LOOK AT EFFICACY IN

1082
00:42:42,319 --> 00:42:46,957
10,000 ADULTS IN INDIA.

1083
00:42:46,957 --> 00:42:49,994
IT'S BEING CONDUCTED BY THE

1084
00:42:49,994 --> 00:42:51,762
INDIAN COUNCIL OF MEDICAL

1085
00:42:51,762 --> 00:42:53,731
RESEARCH, THE ICMR, AND THE

1086
00:42:53,731 --> 00:42:56,400
NATIONAL INSTITUTE OF VIROLOGY

1087
00:42:56,400 --> 00:43:01,038
USING THE P A NACEA PRODUCT, 19

1088
00:43:01,038 --> 00:43:03,774
SITES, 7 OF THOSE SITES HAVE

1089
00:43:03,774 --> 00:43:04,508
BEEN INITIATED.

1090
00:43:04,508 --> 00:43:06,043
THE FIRST DOSE SHOWN HERE WAS

1091
00:43:06,043 --> 00:43:10,381
GIVEN IN THE ROTOX SITE IN THE

1092
00:43:10,381 --> 00:43:11,749
NORTHERN STATE.

1093
00:43:11,749 --> 00:43:13,717
ENROLLMENT CONTINUES AT THE 7

1094
00:43:13,717 --> 00:43:18,255
SITES, ALL 19 SITES SHOULD BE

1095
00:43:18,255 --> 00:43:21,225
ONBOARD BY NOVEMBER AGAIN THEN

1096
00:43:21,225 --> 00:43:22,626
THOUSAND ADULTS AGE 18-60.

1097
00:43:22,626 --> 00:43:24,795
IN THIS TRIAL THEY EXPECT OHM

1098
00:43:24,795 --> 00:43:26,964
ABOUT 10% DENGUE NAIVE EMPLOY SO

1099
00:43:26,964 --> 00:43:28,832
THIS IS A TRIAL THAT IS GOING TO

1100
00:43:28,832 --> 00:43:32,836
TEST AGAIN THE VACCINE EFFICACY

1101
00:43:32,836 --> 00:43:34,671
IN MOSTLY DENGUE EXPOSED

1102
00:43:34,671 --> 00:43:34,972
INDIVIDUALS.

1103
00:43:34,972 --> 00:43:36,240
I'M SURE IT IS GOING TO BE A

1104
00:43:36,240 --> 00:43:37,107
HOME RUN.

1105
00:43:37,107 --> 00:43:40,310
THERE ARE OTHERS WHO ARE

1106
00:43:40,310 --> 00:43:45,249
PLANNING A STUDY IN PEDIATRIC

1107
00:43:45,249 --> 00:43:47,284
POPULATION AND THOSE ARE

1108
00:43:47,284 --> 00:43:47,551
UNDERWAY.

1109
00:43:47,551 --> 00:43:49,553
HOW DID WE GET HERE?

1110
00:43:49,553 --> 00:43:51,422
IT'S ALL ON THE SLIDE, HOW DID

1111
00:43:51,422 --> 00:43:53,957
WE GET HERE IS BY TECHNOLOGY

1112
00:43:53,957 --> 00:43:54,291
TRANSFER.

1113
00:43:54,291 --> 00:43:56,126
WHAT STARTS ON THE BENCH, MOVES

1114
00:43:56,126 --> 00:43:58,662
TO THE BEDSIDE, AND THEN WE MOVE

1115
00:43:58,662 --> 00:44:00,931
INTO IMPLEMENTATION AND I'M

1116
00:44:00,931 --> 00:44:02,766
SHOWING YOU A PHOTO THAT WE

1117
00:44:02,766 --> 00:44:06,236
DISCOVERED FROM 1992 IN THE NIH

1118
00:44:06,236 --> 00:44:11,508
RECORD, THERE'S OUR FRIEND,

1119
00:44:11,508 --> 00:44:15,379
DR. CHEN, BRIAN MURPHY, DONEY

1120
00:44:15,379 --> 00:44:17,681
FAUCI, BOB CHANIC RECEIVING AN

1121
00:44:17,681 --> 00:44:20,150
AWARD, I DON'T KNOW WHAT IT WAS

1122
00:44:20,150 --> 00:44:22,386
FOR BUT I SUSPECT IT WAS WITH

1123
00:44:22,386 --> 00:44:23,087
COLD ADAPTED FLEW.

1124
00:44:23,087 --> 00:44:25,355
THIS IS PETER [INDISCERNIBLE]

1125
00:44:25,355 --> 00:44:28,358
THAT HANDLES MY PORTFOLIO, I AM

1126
00:44:28,358 --> 00:44:29,860
ETERNALLY GRATEFUL FOR ALL THE

1127
00:44:29,860 --> 00:44:31,829
HELP HE PROVIDES IN THIS

1128
00:44:31,829 --> 00:44:32,062
JOURNEY.

1129
00:44:32,062 --> 00:44:35,732
WITHOUT HIM THERE IS NO WAY THIS

1130
00:44:35,732 --> 00:44:37,501
WOULD HAVE BEEN TRANSFERRED TO

1131
00:44:37,501 --> 00:44:40,537
THE DIFFERENT COMPANIES.

1132
00:44:40,537 --> 00:44:44,708
HERE'S A LIST OF THE MOST RECENT

1133
00:44:44,708 --> 00:44:46,643
VACCINE DISCOVERY TEAMS HERE AT

1134
00:44:46,643 --> 00:44:48,946
NIH, WALTER REID, WE HAVE OUR

1135
00:44:48,946 --> 00:44:51,982
CONTRACTORS AT JOHNS HOPKINS

1136
00:44:51,982 --> 00:44:53,317
UNIVERSITY UNIVERSITY OF

1137
00:44:53,317 --> 00:44:56,720
VERMONT, COLLABORATIONS AT UNC,

1138
00:44:56,720 --> 00:45:02,326
LAHOYA ARE FOR TR CELLS MOWBT

1139
00:45:02,326 --> 00:45:04,328
SINAI AND ICCRDBFOR THE

1140
00:45:04,328 --> 00:45:05,929
BANGLADESH STUDY AND AGAIN A

1141
00:45:05,929 --> 00:45:08,232
SHOUT OUT TO THOSE ON THE

1142
00:45:08,232 --> 00:45:09,933
VACCINATION IMPLEMENTATION TEAMS

1143
00:45:09,933 --> 00:45:11,235
INCLUDING [INDISCERNIBLE] HERE

1144
00:45:11,235 --> 00:45:13,904
AT NIH THAT SPONSORS MOST OF OUR

1145
00:45:13,904 --> 00:45:15,072
TRIALS THROUGH CONTRACTS,

1146
00:45:15,072 --> 00:45:17,307
THROUGH OUR VACCINE

1147
00:45:17,307 --> 00:45:20,544
MANUFACTURING AT CRL AND THROUGH

1148
00:45:20,544 --> 00:45:23,480
TTIPO, PETER AND MARRIAN AND OUR

1149
00:45:23,480 --> 00:45:23,881
VACCINE LICENSEES.

1150
00:45:23,881 --> 00:45:24,915
THANK YOU VERY MUCH FOR YOUR

1151
00:45:24,915 --> 00:45:25,182
ATTENTION.

1152
00:45:25,182 --> 00:45:27,384
HAPPY TO ANSWER QUESTIONS.

1153
00:45:27,384 --> 00:45:37,628
[ APPLAUSE ] 

1154
00:45:40,764 --> 00:45:41,832
>> OF COURSE MICs FOR

1155
00:45:41,832 --> 00:45:45,002
QUESTIONS, BUT I DO HAVE 1

1156
00:45:45,002 --> 00:45:47,137
ONLINE TO GET THE QUESTIONS

1157
00:45:47,137 --> 00:45:49,306
GOING, DO SKIN PUOF THULES

1158
00:45:49,306 --> 00:45:49,973
CONTAIN LIVE VIRUS?

1159
00:45:49,973 --> 00:45:50,774
>> THEY DO NOT.

1160
00:45:50,774 --> 00:45:53,544
SO WE HAVE DONE PUNCH BIOPSIES

1161
00:45:53,544 --> 00:45:54,811
TO ANSWER THAT QUESTION.

1162
00:45:54,811 --> 00:45:56,113
WE THINK IT'S IMMUNE RESPONSE

1163
00:45:56,113 --> 00:45:59,516
BUT WE HAVE PUNCHED A LOT OF

1164
00:45:59,516 --> 00:46:00,918
VOLUNTEERS AND HAVE TO THE BEEN

1165
00:46:00,918 --> 00:46:04,154
ABLE TO DETECT VIRUS IN THE

1166
00:46:04,154 --> 00:46:08,959
APPLIED P A PULES.

1167
00:46:08,959 --> 00:46:10,494
>> BEAUTIFUL TALK STEPHEN,
AND

1168
00:46:10,494 --> 00:46:12,296
IT REALLY SHOWS IT'S IMPORTANT

1169
00:46:12,296 --> 00:46:13,564
TO SWEAT THE DETAILS THAT IT IS

1170
00:46:13,564 --> 00:46:17,634
TO TEST ALL THESE THINGS YOU

1171
00:46:17,634 --> 00:46:18,936
KNOW HUNDREDS OF CONSTRUCTS TO

1172
00:46:18,936 --> 00:46:20,671
FIND THE OPTIMAL THING.

1173
00:46:20,671 --> 00:46:22,406
WITH LIVE VACCINES, THERE'S

1174
00:46:22,406 --> 00:46:24,775
ALWAYS CONCERNS ABOUT STABILITY

1175
00:46:24,775 --> 00:46:27,177
WHEN IT GOES THROUGH INDIVIDUAL

1176
00:46:27,177 --> 00:46:28,178
OR MOSQUITO, WONDER IF YOU COULD

1177
00:46:28,178 --> 00:46:29,580
COMMENT ON THAT AND THE OTHER

1178
00:46:29,580 --> 00:46:31,448
QUESTION IS ABOUT IMMUNO

1179
00:46:31,448 --> 00:46:35,986
COMPROMISED HOSTS GETTING LIVE

1180
00:46:35,986 --> 00:46:36,820
VACCINES.

1181
00:46:36,820 --> 00:46:37,487
>> TWO EXCELLENT
QUESTIONS, I'M

1182
00:46:37,487 --> 00:46:40,023
SORRY I DIDN'T HAVE TIME TO TALK

1183
00:46:40,023 --> 00:46:43,694
ABOUT WHAT WE LOOKED AT FOR

1184
00:46:43,694 --> 00:46:44,695
MOSQUITO TRANSMISSIBILITY OF THE

1185
00:46:44,695 --> 00:46:45,529
VIRUS.

1186
00:46:45,529 --> 00:46:47,264
SO THE PRINCIPLE ATTENUATING

1187
00:46:47,264 --> 00:46:49,199
MUTATION IS THAT DELTA 3

1188
00:46:49,199 --> 00:46:51,201
MUTATION IN A 3 PRIME UTR.

1189
00:46:51,201 --> 00:46:53,503
WE HAVE MANY, MANY ISOLATES FROM

1190
00:46:53,503 --> 00:46:57,674
VOLUNTEERS AT LATE DATES.

1191
00:46:57,674 --> 00:47:00,210
THEIR LAST DAY OF VIREMIA, WE

1192
00:47:00,210 --> 00:47:02,512
HAVE LOOKED AT THOSE VIRUS

1193
00:47:02,512 --> 00:47:04,748
SEQUENCES, 3 PRIME UTR, WE DON'T

1194
00:47:04,748 --> 00:47:05,582
SEE ENLARGE.

1195
00:47:05,582 --> 00:47:06,850
OR CONSTRICTURE OF THAT MUTATION

1196
00:47:06,850 --> 00:47:08,752
SO WE CONSIDER THAT STABLE.

1197
00:47:08,752 --> 00:47:11,788
THAT DELTA 30 MUTATION DOES

1198
00:47:11,788 --> 00:47:15,759
BLOCK INFECTION FELT VIRUSES IN

1199
00:47:15,759 --> 00:47:16,360
MOSQUITOES.

1200
00:47:16,360 --> 00:47:18,829
SO FOR MOSQUITOES THAT WERE

1201
00:47:18,829 --> 00:47:20,697
BLOOD FED BLOOD MEAL CONTAINING

1202
00:47:20,697 --> 00:47:22,432
VACCINES WE SEE RESTRICTED

1203
00:47:22,432 --> 00:47:23,834
REPLICATION AND THERE ARE

1204
00:47:23,834 --> 00:47:25,235
SEVERAL BLOCKS IN MOSQUITOES AND

1205
00:47:25,235 --> 00:47:28,238
IT'S DIFFERENT FOR THE DIFFERENT

1206
00:47:28,238 --> 00:47:29,606
SEROTYPES OR VIRUSES, SO SOME OF

1207
00:47:29,606 --> 00:47:33,677
THEM ARE BLOCKED IN THEIR

1208
00:47:33,677 --> 00:47:35,178
ABILITY TO AFFECT MIDGUT, SOME

1209
00:47:35,178 --> 00:47:37,681
AFFECT THE MIDGUT BUT DO NOT

1210
00:47:37,681 --> 00:47:40,851
ESCAPE FROM THE MIDGUT INTO THE

1211
00:47:40,851 --> 00:47:42,019
HEMOLIMP, SOME OF THEM YOU CAN

1212
00:47:42,019 --> 00:47:43,320
FIND IN THE HEESM O LIMP BUT

1213
00:47:43,320 --> 00:47:47,324
THEY DO NOT AFFECT THE SALIVARY

1214
00:47:47,324 --> 00:47:49,860
GLANDS SO INTRINSICALLY THEY'RE

1215
00:47:49,860 --> 00:47:50,927
NOT TRANSMISSIBLE BY MOSQUITO.

1216
00:47:50,927 --> 00:47:53,030
GIVEN THAT WE VACCINATED

1217
00:47:53,030 --> 00:47:55,666
INDIVIDUALS ON DAY, 6, 7, AND 8,

1218
00:47:55,666 --> 00:47:57,434
PEAK DAYS OF VIREMIA, AND WE FED

1219
00:47:57,434 --> 00:47:59,836
MODEL CITIZEN QUEET OS ON THEIR

1220
00:47:59,836 --> 00:48:01,204
ARM, TOOK THEM BACK TO THE LAB,

1221
00:48:01,204 --> 00:48:03,407
GREW THEM UP AND IN NO CASE DID

1222
00:48:03,407 --> 00:48:05,275
WE HAVE AN INFECTED MOSQUITO

1223
00:48:05,275 --> 00:48:07,344
THAT IS BECAUSE I SHOWED THE

1224
00:48:07,344 --> 00:48:09,746
LEVEL OF VIREMIA IS VERY LOW,

1225
00:48:09,746 --> 00:48:11,515
LESS THAN 10 PFU, WHICH IS NOT

1226
00:48:11,515 --> 00:48:13,383
ENOUGH EVEN IF IT WAS VIRULENT

1227
00:48:13,383 --> 00:48:15,018
TO TRANSMIT TO A MOSQUITO.

1228
00:48:15,018 --> 00:48:17,621
AND THE OTHER QUESTION WAS

1229
00:48:17,621 --> 00:48:18,689
IMMUNO COMPROMISE.

1230
00:48:18,689 --> 00:48:21,992
DENGUE IS NOT A SPECIFIC

1231
00:48:21,992 --> 00:48:23,660
ENHANCED DANGER IN IMMUNO

1232
00:48:23,660 --> 00:48:24,161
COMPROMISED INDIVIDUALS.

1233
00:48:24,161 --> 00:48:28,098
IN MANY OF THESE COUNTRIES WHERE

1234
00:48:28,098 --> 00:48:29,499
IT'S TRANSMITTED NATURALLY, YOU

1235
00:48:29,499 --> 00:48:34,705
DON'T SEE AN UPTICK IN IMMUNO

1236
00:48:34,705 --> 00:48:37,607
 IMMUNO

1237
00:48:37,607 --> 00:48:38,542
COMPROMISED PATIENTS WITH DENGUE

1238
00:48:38,542 --> 00:48:38,809
DISEASE.

1239
00:48:38,809 --> 00:48:40,644
WE WOULD LOVE TO TEST THIS IN A

1240
00:48:40,644 --> 00:48:40,844
STUDY.

1241
00:48:40,844 --> 00:48:42,879
IF WE HAD THE MONEY TO DO IT, WE

1242
00:48:42,879 --> 00:48:44,414
WOULD BE DOING THAT STUDY AT

1243
00:48:44,414 --> 00:48:45,382
JOHNS HOPKINS BUT IT'S A

1244
00:48:45,382 --> 00:48:48,318
QUESTION THAT NEEDS TO BE

1245
00:48:48,318 --> 00:48:51,455
ANSWERED, SURE.

1246
00:48:51,455 --> 00:48:52,622
NDR. WHITEHEAD YOUR AGGREGATE

1247
00:48:52,622 --> 00:48:53,357
DATA IS INCREDIBLE.

1248
00:48:53,357 --> 00:48:54,791
SIGN ME UP.

1249
00:48:54,791 --> 00:48:57,994
BUT WHEN I'M THINKING ABOUT

1250
00:48:57,994 --> 00:48:59,196
ESSENTIALLY ASKING FOR VIRUSES

1251
00:48:59,196 --> 00:49:01,064
TO INFECT AT THE SAME TIME, WHEN

1252
00:49:01,064 --> 00:49:03,967
YOU TEASE OUT ARE YOU SEEING

1253
00:49:03,967 --> 00:49:04,568
BOTTLENECK EFFECTS?

1254
00:49:04,568 --> 00:49:06,737
AND HAVE YOU ADJUSTED THE RATIOS

1255
00:49:06,737 --> 00:49:09,573
AND THE VACCINE OR ANYTHING TO

1256
00:49:09,573 --> 00:49:12,275
ADAPT TO THOSE NEEDS?

1257
00:49:12,275 --> 00:49:13,810
>> THAT IS ALSO AN
EXCELLENT

1258
00:49:13,810 --> 00:49:14,077
QUESTION.

1259
00:49:14,077 --> 00:49:16,179
SO AS I TOLD YOU EARLIER, EACH

1260
00:49:16,179 --> 00:49:19,349
OF THOSE VIRUSES IS DELIVERED AT

1261
00:49:19,349 --> 00:49:22,219
A THOUSAND PFUs, SO YOU'RE

1262
00:49:22,219 --> 00:49:26,089
GIVING 4000 PFU, THAT

1263
00:49:26,089 --> 00:49:28,058
DOESN'T--THE MOI IF YOU WILL,

1264
00:49:28,058 --> 00:49:30,026
AND THE INJECTION SITE IS STILL

1265
00:49:30,026 --> 00:49:31,261
VERY, VERY LOW.

1266
00:49:31,261 --> 00:49:33,997
SO WE DON'T SUSPECT THAT WE'RE

1267
00:49:33,997 --> 00:49:35,732
EVEN GETTING DOUBLY INFECTED

1268
00:49:35,732 --> 00:49:36,466
CELLS.

1269
00:49:36,466 --> 00:49:38,068
SO WE DON'T--WE DON'T THINK IT'S

1270
00:49:38,068 --> 00:49:39,503
A PROBLEM WITH INTERFERENCE, AND

1271
00:49:39,503 --> 00:49:42,239
IF YOU GO BACK TO THE OLD

1272
00:49:42,239 --> 00:49:44,341
LITERATURE YOU HEAR A LOT ABOUT

1273
00:49:44,341 --> 00:49:48,645
VIRAL INTERFERENCE AND THIS IS

1274
00:49:48,645 --> 00:49:51,348
MOSTLY FROM EARLY TRIALS WHICH

1275
00:49:51,348 --> 00:49:52,749
THEY ATTRIBUTED THE FACT THAT

1276
00:49:52,749 --> 00:49:54,384
THEY WEREN'T SEEING GOOD

1277
00:49:54,384 --> 00:49:56,286
IMMUNITY TO SOME SEROTYPES AS

1278
00:49:56,286 --> 00:49:57,454
VIRAL INTERFERENCE, I BELIEVE IT

1279
00:49:57,454 --> 00:49:59,556
WAS JUST THESE VIRUSES WERE NOT

1280
00:49:59,556 --> 00:50:01,725
INFECTING, SO I'M NOT A BIG

1281
00:50:01,725 --> 00:50:04,161
BELIEVER IN THIS VIRAL IRPT FER

1282
00:50:04,161 --> 00:50:06,363
ENSEL, WE HAD A DENGUE 3

1283
00:50:06,363 --> 00:50:07,564
CANDIDATE WHICH IS CHIMERIC THAT

1284
00:50:07,564 --> 00:50:10,867
WHEN WE TESTED IT, IN HUMANS, WE

1285
00:50:10,867 --> 00:50:14,104
GOT VERY LOW LEVELS OF

1286
00:50:14,104 --> 00:50:15,071
INFECTIVITY, VERY LOW IMMUNO

1287
00:50:15,071 --> 00:50:19,009
GENERATEDISSITY, IF WE HAD PUT

1288
00:50:19,009 --> 00:50:20,610
THAT IN A TETRAVALENTINEDDENT

1289
00:50:20,610 --> 00:50:23,079
FORMULATION WITH THIS RATHER

1290
00:50:23,079 --> 00:50:24,648
POORLY INFECTIOUS DENGUE 3 AND

1291
00:50:24,648 --> 00:50:26,516
GIVEN THAT EARLY AT THE TURN OF

1292
00:50:26,516 --> 00:50:27,717
THE CENTURY, THAT'S WHAT WHY

1293
00:50:27,717 --> 00:50:30,720
KIDS CALL IT, YOU KNOW THE EARLY

1294
00:50:30,720 --> 00:50:32,989
2000S, WE WOULD HAVE SAID

1295
00:50:32,989 --> 00:50:35,158
SOMETHING'S WRONG WITH DENGUE 3.

1296
00:50:35,158 --> 00:50:36,593
IT MUST BE INTERFERENCE BUT I

1297
00:50:36,593 --> 00:50:38,295
REALLY DON'T THINK THAT'S

1298
00:50:38,295 --> 00:50:39,696
PLAYING A ROLE IN THIS.

1299
00:50:39,696 --> 00:50:43,533
I DON'T THINK THERE'S A

1300
00:50:43,533 --> 00:50:44,334
BOTTLENECK.

1301
00:50:44,334 --> 00:50:45,335
NOW, WE INITIALLY THOUGHT THAT

1302
00:50:45,335 --> 00:50:46,803
MAYBE DENGUE FOCUSED ON IS A

1303
00:50:46,803 --> 00:50:47,737
LITTLE LESS INFECTIOUS AND WE

1304
00:50:47,737 --> 00:50:49,739
GAVE THAT AT A HIGHER DOSE, SO,

1305
00:50:49,739 --> 00:50:54,945
WE HAD A FORMULATION CALLED

1306
00:50:54,945 --> 00:50:58,315
TB005 WHICH WAS 3-4 LOGS FOR

1307
00:50:58,315 --> 00:51:00,517
DENGUE 2, 3 AND FOR DENGUE 32

1308
00:51:00,517 --> 00:51:01,585
EXPE 4.

1309
00:51:01,585 --> 00:51:03,353
WE SAW A BIT OF AN IMPROVEMENT

1310
00:51:03,353 --> 00:51:05,055
BUT AS WE EXPANDED THOSE STUDIES

1311
00:51:05,055 --> 00:51:07,157
IT REALLY DID NOT MAKE A BIG

1312
00:51:07,157 --> 00:51:08,425
DIFFERENCE AND WHEN YOU ARE

1313
00:51:08,425 --> 00:51:11,595
GOING TO INCREASE THE POTENCY 10

1314
00:51:11,595 --> 00:51:15,232
FOLD THAT HAS A HUGE IMPACT ON

1315
00:51:15,232 --> 00:51:16,867
MANUFACTURING CAPABILITIES.

1316
00:51:16,867 --> 00:51:17,834
SO TB0 WHERE ARE 3 IS WHAT

1317
00:51:17,834 --> 00:51:20,670
EVERYBODY IS MOVING FORWARD WITH

1318
00:51:20,670 --> 00:51:23,173
AT THIS TIME.

1319
00:51:23,173 --> 00:51:24,107
>> THANK YOU.

1320
00:51:24,107 --> 00:51:25,509
>> HI, STEVE WHAT AN
INSPIRING

1321
00:51:25,509 --> 00:51:25,709
TALK.

1322
00:51:25,709 --> 00:51:27,244
GREAT TO SEE IT ALL LAID OUT.

1323
00:51:27,244 --> 00:51:28,979
MY QUESTION WAS ABOUT EFFICACY

1324
00:51:28,979 --> 00:51:30,714
OVER TIME AND THE DECREASE THAT

1325
00:51:30,714 --> 00:51:34,150
YOU SEE WITH ALL 3 VACCINES

1326
00:51:34,150 --> 00:51:38,889
ESPECIALLY JUST AGAINST

1327
00:51:38,889 --> 00:51:40,156
INFECTION THE CEIVERRITY

1328
00:51:40,156 --> 00:51:41,491
MAINTAINS THE PROTECTION, SO I

1329
00:51:41,491 --> 00:51:43,560
WAS WONDERING IF THAT'S THE

1330
00:51:43,560 --> 00:51:44,828
PLACEBO GROUP GETTING MORE

1331
00:51:44,828 --> 00:51:46,229
INFEBTED OR IF THEY'RE PROTECTED

1332
00:51:46,229 --> 00:51:47,664
RELATIVE TO THE VACCINE GROUP OR

1333
00:51:47,664 --> 00:51:49,866
IF YOU THINK THERE'S SOMETHING

1334
00:51:49,866 --> 00:51:51,968
BIOLOGICAL AND A 5 YEAR BOOST

1335
00:51:51,968 --> 00:51:54,437
MIGHT BE RECOMMENDED AT SOME

1336
00:51:54,437 --> 00:51:54,638
POINT?

1337
00:51:54,638 --> 00:51:56,306
>> THAT'S A GOOD QUESTION.

1338
00:51:56,306 --> 00:51:57,707
THE MOST COMMON QUESTION WE ARE

1339
00:51:57,707 --> 00:51:59,743
ASKED IS WHEN WILL YOU NEED TO

1340
00:51:59,743 --> 00:52:01,044
BE BOOSTED?

1341
00:52:01,044 --> 00:52:03,146
NOW A YELLOW FEVER VACCINE, THEY

1342
00:52:03,146 --> 00:52:04,347
KEEP CHANGING, YOU YOU NEED A

1343
00:52:04,347 --> 00:52:05,815
BOOST AT 10 YEARS, YOU DON'T

1344
00:52:05,815 --> 00:52:08,285
NEED A BOOST AT 10 YEARS, IT'S

1345
00:52:08,285 --> 00:52:08,885
LIFE LONG IMMUNITY.

1346
00:52:08,885 --> 00:52:12,622
WE BELIEVE IF WE ARE LOOKING FOR

1347
00:52:12,622 --> 00:52:13,323
EFFICACY AGAINST SERIOUS DENGUE

1348
00:52:13,323 --> 00:52:15,225
AND I SHOWED YOU THAT, WE REALLY

1349
00:52:15,225 --> 00:52:18,061
DEPARTMENT SEE A DECREASE IN

1350
00:52:18,061 --> 00:52:19,029
SERIOUS DENGUE, BUT IN THE

1351
00:52:19,029 --> 00:52:20,230
CLINICAL TRIALS WHERE YOU ARE

1352
00:52:20,230 --> 00:52:22,399
CAPTURING ALL THE CASES,

1353
00:52:22,399 --> 00:52:25,235
ACCORDING TO YOUR CASE

1354
00:52:25,235 --> 00:52:27,470
DEFINITION, YOU DO SEE A

1355
00:52:27,470 --> 00:52:28,038
DECREASE OVER TIME.

1356
00:52:28,038 --> 00:52:35,378
WHEN WILL THEY NEED TO BE

1357
00:52:35,378 --> 00:52:35,612
BOOSTED?

1358
00:52:35,612 --> 00:52:37,213
WELL, EVENTUALLY WE BELIEVE IF

1359
00:52:37,213 --> 00:52:39,983
YOU ARE LIVING IN AN ENDEMIC

1360
00:52:39,983 --> 00:52:42,085
AREA, YOUR CIRCULATING IMMUNITY,

1361
00:52:42,085 --> 00:52:43,219
YOUR CIRCULATING ANTIBODIES WILL

1362
00:52:43,219 --> 00:52:45,488
PROBABLY WANE TO A LEVEL WHICH

1363
00:52:45,488 --> 00:52:47,223
WILL ALLOW A NATURAL INFECTION,

1364
00:52:47,223 --> 00:52:49,626
AND YOU WILL PROBABLY BOOST, YOU

1365
00:52:49,626 --> 00:52:51,461
WON'T EVEN RECOGNIZE NAAS AN

1366
00:52:51,461 --> 00:52:53,797
INFECTION BECAUSE IT WILL BE

1367
00:52:53,797 --> 00:52:54,798
ASYMPTOMATIC.

1368
00:52:54,798 --> 00:52:57,601
THAT'S WHAT HAPPENS IN ENDEMIC

1369
00:52:57,601 --> 00:52:57,801
AREA.

1370
00:52:57,801 --> 00:52:59,803
PEOPLE LIKE ME WHO LIVE IN THE

1371
00:52:59,803 --> 00:53:00,870
U.S. AND GET VACCINATED BECAUSE

1372
00:53:00,870 --> 00:53:03,406
I WANT TO GO ON A TRIP, WE MAY

1373
00:53:03,406 --> 00:53:05,842
NEED A BOOSTER BECAUSE WE'RE NOT

1374
00:53:05,842 --> 00:53:06,509
NATURALLY EXPOSED.

1375
00:53:06,509 --> 00:53:06,977
GOOD QUESTION.

1376
00:53:06,977 --> 00:53:08,812
THAT IS SOMETHING THANKFULLY

1377
00:53:08,812 --> 00:53:09,846
THAT OUR PHARMACEUTICAL PARTNERS

1378
00:53:09,846 --> 00:53:14,751
WILL HAVE TO LOOK AT IN THEIR

1379
00:53:14,751 --> 00:53:19,155
PHASE 4 POST MARKETING PROJECTS.

1380
00:53:19,155 --> 00:53:23,059
NI HAVE ANOTHER QUESTION ONLINE,

1381
00:53:23,059 --> 00:53:24,861
SOMEWHAT PHILOSOPHICAL.

1382
00:53:24,861 --> 00:53:25,762
HAS ANYONE COMPARED THEEC

1383
00:53:25,762 --> 00:53:26,863
NATIONAL LIBRARY OF

1384
00:53:26,863 --> 00:53:28,331
MEDICINICICAL IMPLICATION OF

1385
00:53:28,331 --> 00:53:35,538
GENERATING THESE VACCINES VERSUS

1386
00:53:35,538 --> 00:53:37,507
ERADICATE MOSQUITOES?

1387
00:53:37,507 --> 00:53:38,008
[LAUGHTER]

1388
00:53:38,008 --> 00:53:39,542
>> ERADICATING MOSQUITOES,
WOULD

1389
00:53:39,542 --> 00:53:40,644
BE MY PREFERENCE.

1390
00:53:40,644 --> 00:53:41,111
HONESTLY.

1391
00:53:41,111 --> 00:53:44,914
>> ON THE RECORD OF
COURSE.

1392
00:53:44,914 --> 00:53:45,649
>> IS THAT POSSIBLE?

1393
00:53:45,649 --> 00:53:46,416
I DON'T KNOW.

1394
00:53:46,416 --> 00:53:49,953
I THINK VACCINATION IS MORE

1395
00:53:49,953 --> 00:53:51,521
POSSIBLE THAN ERADICATING

1396
00:53:51,521 --> 00:53:51,955
MOSQUITOES.

1397
00:53:51,955 --> 00:53:54,658
HAS THERE BEEN AN ECONOMIC

1398
00:53:54,658 --> 00:53:55,458
COMPARISON?

1399
00:53:55,458 --> 00:53:56,660
I'M NOT SURE.

1400
00:53:56,660 --> 00:54:00,397
I WILL TELL YOU A LITTLE

1401
00:54:00,397 --> 00:54:02,565
ANECDOTE, WE DID A VERY STUDY

1402
00:54:02,565 --> 00:54:04,567
EARLY IN WITH WALTER REID WHERE

1403
00:54:04,567 --> 00:54:06,803
SOME OF THE SCHOOLS IN THEIR

1404
00:54:06,803 --> 00:54:10,440
CLINICAL SITE HAD A LOT OF

1405
00:54:10,440 --> 00:54:10,974
DENGUE.

1406
00:54:10,974 --> 00:54:13,043
THEY WENT IN AND THEY SPRAYED

1407
00:54:13,043 --> 00:54:14,244
THESE SCHOOLS AND THEY PUT

1408
00:54:14,244 --> 00:54:17,080
SCREENS ON THE WINDOWS, DENGUE

1409
00:54:17,080 --> 00:54:18,782
INCIDENT WENT DOWN THE VERY

1410
00:54:18,782 --> 00:54:19,449
FIRST YEAR.

1411
00:54:19,449 --> 00:54:23,520
THE SECOND YEAR IT WENT DOWN.

1412
00:54:23,520 --> 00:54:24,721
THEN, MM, WE'RE NOT HAVING

1413
00:54:24,721 --> 00:54:26,756
DENGUE, WE'RE NOT GOING TO

1414
00:54:26,756 --> 00:54:26,990
SPRAY.

1415
00:54:26,990 --> 00:54:28,758
AND WE HATE THE SCREENS, IT

1416
00:54:28,758 --> 00:54:30,827
DOESN'T LET THE AIR FLOW

1417
00:54:30,827 --> 00:54:32,462
THROUGH, SO NO SPRAYING, THE

1418
00:54:32,462 --> 00:54:33,663
KREENS CAME DOWN, DENGUE CAM

1419
00:54:33,663 --> 00:54:37,367
BACK THE FOLLOWING YEAR.

1420
00:54:37,367 --> 00:54:40,770
SO FOR MOSQUITO ERADICATION, IT

1421
00:54:40,770 --> 00:54:43,139
WORKS BUT SUSTAINABILITY IS

1422
00:54:43,139 --> 00:54:45,675
ALWAYS THE ISSUE, UNFORTUNATELY.

1423
00:54:45,675 --> 00:54:47,610
>> THERE ALREADY WAS AN
EFFORT

1424
00:54:47,610 --> 00:54:58,121
IN LATIN AMERICA TO ERADICATE

1425
00:54:58,722 --> 00:55:02,392
THE AEDES EJIPTI MOSQUITO.

1426
00:55:02,392 --> 00:55:06,296
>> FRED DID A GREAT JOB

1427
00:55:06,296 --> 00:55:07,564
ERADICATING MOSQUITOES UNTIL DDT

1428
00:55:07,564 --> 00:55:09,899
WAS TAKEN AWAY FROM HIM, BUT

1429
00:55:09,899 --> 00:55:10,500
THAT'S ANOTHER STORY.

1430
00:55:10,500 --> 00:55:18,108
GOOD COMMENT. 

1431
00:55:18,108 --> 00:55:18,441
THANK YOU.

1432
00:55:18,441 --> 00:55:18,908
>> [INDISCERNIBLE]

1433
00:55:18,908 --> 00:55:20,443
>> WE WILL HAVE A
RECEPTION AT

1434
00:55:20,443 --> 00:55:21,144
THE LIBRARY AFTER.

1435
00:55:21,144 --> 00:55:23,012
IF YOU HAVE ADDITIONAL

1436
00:55:23,012 --> 00:55:24,180
QUESTIONS, VERY, VERY HAPPY TO

1437
00:55:24,180 --> 00:55:27,851
SPEAK WITH YOU AT THAT.

1438
00:55:27,851 --> 00:55:28,118
NINA?

1439
00:55:28,118 --> 00:55:30,453
>> GREAT, WELL, THANK YOU
SO

1440
00:55:30,453 --> 00:55:32,188
MUCH DR. WHITEHEAD AND

1441
00:55:32,188 --> 00:55:37,060
CONGRATULATIONS REALLY, REALLY

1442
00:55:37,060 --> 00:55:38,428
FANTASTIC FROM THE LABORATORY TO

1443
00:55:38,428 --> 00:55:40,463
THE INDIVIDUAL CLINICAL STUDY

1444
00:55:40,463 --> 00:55:42,632
AND HOPEFULLY OUT TO COMMUNITIES

1445
00:55:42,632 --> 00:55:45,702
AROUND THE WORLD AND DR. CHEN, I

1446
00:55:45,702 --> 00:55:49,773
THINK YOU SEE THAT YOUR LEGACY

1447
00:55:49,773 --> 00:55:51,775
IS NOT JUST TO NIH, IT IS TO THE

1448
00:55:51,775 --> 00:55:54,611
WORLD THROUGH ALL OF THOSE

1449
00:55:54,611 --> 00:55:56,780
YOU'VE EMPOWERED AND REALLY WE

1450
00:55:56,780 --> 00:55:58,481
ARE SO GRATEFUL FOR EVERYTHING

1451
00:55:58,481 --> 00:55:58,948
YOU'VE DONE.

1452
00:55:58,948 --> 00:56:01,384
SO THANK YOU ALL FOR BEING HERE

1453
00:56:01,384 --> 00:56:03,119
WITH US.

1454
00:56:03,119 --> 00:56:04,187
[ APPLAUSE ]

1455
00:56:04,187 --> 00:56:14,464
>> THANK YOU.

1456
01:58:01,434 --> 01:58:11,410