>> WELL, LET ME WELCOME YOU TO

TODAY'S DIRECTORS LECTURE FROM

JESUS VALENZUELA, WHO IS CHIEF

OF BACTERIAL AND MOLECULAR

INFECTION AT THE VECTOR

INSTITUTE.

HE GOT HIS Ph.D. FROM THE

UNIVERSITY OF ARIZONA AND DID

POST DOCTORAL WORK AT NIAID IN

THE LABORATORY OF PARASITIC

DISEASES AND BECAME A RESEARCH

FELLOW AND FINALLY IN 2002,

BECAME AN INVESTIGATOR IN THE

LABORATORY OF MALARIA AND VECTOR

AND WERE WAS TENURED A COUPLE

YEARS AGO BY THE NIH CENTRAL

TENURE COMMITTEE.

HE'S BEEN INTERESTED IN

PARASITIC DISEASES INCLUDING

MALARIA, AND MONASIS, AND HAS

BEEN ROLL IN THE INSECT VECTORS

AND SAIL--SALIVARY GRAND AND GUT

AND TRANSMISSION PART OF THIS

DISEASE.

HIS TITLE IS:  BASIC AND

TRANSLATIONAL RESEARCH FROM SAN

FRANCISCO LIVA FROM INSECT

TECT--VECTORS FROM PHARMACOLOGY

AND BY O VACCINES.

JESUS?

>> THANK YOU DR. GOTTESMAN FOR

THE GREAT INTRODUCTION AND THANK

YOU FOR COMING AND I THINK THE

ROCKY MOUNTAIN LABS ALSO MIGHT

BE WATCHING THIS TALK, HELLO?

AND TODAYED I'LL TALK ABOUT AS

THE DOCTOR WAS SAYING ABOUT SAN

FRANCISCO SALIVA--SALIVA OF

INSECT.

I'LL TRY TO CONVEY A MESSAGE

ABOUT WHY I'M INTERESTED IN THE

SALIVA AND VICT VECTOR BORN

INSECT DISEASES AND I WILL TRY

TO GIVE A BIT OF HISTORY ABOUT

MY RESEARCH AND TO WHAT WE'RE

CURRENTLY DOING WHICH IS

BIOMARKER AND BIOVACCINES BUT

SCIENCE IS QUITE INTERESTING

BECAUSE I CAN GO BACK TO SOME OF

THE PHARMACOLOGY COMPONENTS TO

DO THE REST OF THE MOLECULE, OF

THE ADVANCES IN THE LAB.

OOPS, LET'S SEE IF WE CAN CHANGE

THIS.

WHEN WE TALK ABOUT VECTOR BORN

DISEASES IN WHICH WE WILL BE

DISCUSSING TODAY, WE THINK ABOUT

THE INTERACTION BETWEEN THE

PATHOGEN AND THE HOST AND

ACTUALLY MOST OF RESEARCH HAS

BEEN DONE IN THIS AREA,

PATHOGENS AND HOST, AND HOUSE

RESPONSE TO PATHOGENS.

THERE'S MORE WORK DONE BY

DIFFERENT LABS INCLUDING OURS

INCLUDING INTERACTIONS OF THE

PATHOGEN IN THE VECTOR BUT MUCH

LESS IN THE INTERACTIONS BETWEEN

THE VECTOR AND THE HOST AND THIS

IS WHAT I'M GOING TO EMPHASIZE

TO THIS INTERACTION OF HOW THIS

INTERACTIONS FROM THE VECTOR

SALIVA CAN AFFECT THE HOST, CAN

AFFECT THE PARASITE, AND

ULTIMATELY AFFECTED THE DISEASE

THAT IS TRANSMITTED BY THIS

VECTOR.

DRNCHL AND 1 POINT, I WANT TO

MAKE, WE'RE ALSO VERY MUCH

INTERESTED IN EMPHASIZING GLOBAL

HEALTH AND PARTICULARLY

NEGLECTED DISEASES AND THIS IS

SOMETHING WE SRO MENTIONED IN

THE LAB, PARTICULARLY WHERE THEY

ARE WORKING ON AND THE

COLLABORATORS WHERE WE HAVE

ENCOULD YOU WANTER INNED THE

LAST FEW YEARS AND JUST TO GIVE

YOU A NUMBER, 50% OF NEGLECTED

TROPICAL DISEASES ARE VECTOR

BORN.

THAT'S WHY VECTORS ARE ALSO VERY

RELEVANT FOR THE DISEASES, THAT

WE NEED TO TARGET AND TALK ABOUT

NEGLECTED VECTOR DISEASE, I AM

EMPHASIZE 1, WHICH IS THE 1 WE

ARE TODAYING IN THE LAB WHICH IS

IS THE LIESHMANNIA AND THIS IS

IMPORTANT DUE TO THE RECENT

NUMBERS OF B-SELMANIA SIS IN

SUDAN AND ALSO INDIA AND THE„i

THE--CAUSED BY DIFFERENT

PARASITES, THE FORMS WE HAVE THE

SUBCUTANEOUS FORM OF LEASH MAN

ICEIS

DRNCHL--LEISHMANIASES AND THIS

IS A VERY SMALL PICTURE OF THE

LIFE CYCLE BUT I WANT TO STRESS

SOMETHING VERY IMPORTANT HERE,

WHEN WE TALK ABOUT

LEISHMANIASES, THERE ARE 2

HOSTS, WE HAVE THE VECTOR IN

WHICH THE PARASITE USES THE SITE

TO GO OUT TO THE FORM TOED

METACYCLIC FORM, THE VECTOR IS

ANi1

INFECTIVE FORMS OF THE PARASITE

AND THEN THERE'S THE PARASITE

THAT GOES INTO THE MAMMALIAN

HOST AND GOES INTO MACROFAGSS

AND GET THE--MAKE ROW FASHIONS

AGAIN AND THEY GET INFECTIONS.

NOW THIS IS THE POINT, THE

MESSAGE TODAY, HOW IMPORTANT IN

THIS CYCLE SALIVA IS AND HOW

WE'RE USING SALIVA NOT ONLY

FOR--I WILL GIVE OTHER EXAMPLES

OF THE PHARMACOLOGY AND ALL THE

BIOLOGICAL MARKERS AND ALSO

POTENTIAL VACCINES TO PREVENT

THIS PARTICULAR DISEASE.

I JUST REALIZE YESTERDAY WHEN I

WAS LOOKING AT THE QUIRES AND

HOW MANY YEARS I'VE BEEN IN

SALIVA WORK, IT'S 18 YEARS.

I WAS LIKE, OH MY GOSH, ALMOST

THE SAME TIME I'VE BEEN MARRIED

TO MY WIFE.

DANA'S LIKE SO FAR SO GOOD IN

BOTH FIELDS.

AND WHAT AMAZED ME IS LIKE, WHY

AM I SO INTERESTED WITH SALIVA

AFTER 18 YEARS IN AND THE ANSWER

THAT MANY, AT THE END OF THE

TALK YOU WILL SEE WHY ACCIDENT

BUT WHY I'M ALWAYS IMPRESS WIDE

THE SALIVA IS IT COMES IN THIS

SLIDE, IT'S NOT VERY COMPLEX.

THERE ARE ONLY FEW PROBLEMS,

THERE ARE ABOUT 20 TO 30

PROBLEMS WITH THE SALIVA AT

LEAST WITH SAND FLIES, THE TOTAL

AMOUNT OF PROTEIN IN 1 GRAM AND

1 MICROGRAM.

NOW EVERY TIME THAT A SAND FLY

TAKES A MEAL TRELEASES ONLY A

PROPORTION OF IS 1 FIFTH OR--I

DON'T KNOW THE NUMBER BUT IT IS

A PROPORTION.

WHICH MEANS THAT EVERY TIME IT'S

IN FLIGHT IT INGESTS THESE

PROTEINS AND IF WE CALCULATE

THESE NANO GRAMS, DIVIDED BY

SOME 30 PROTEINS, WE'RE TALKING

ABOUT INJECTION OF FEW NANO

GRAMS TO HIGH PICO GRAMS, THAT

AMOUNT OF PROTEIN IS ENOUGH TO

CHANGE OUR PHYSIOLOGY.

I'M GOING TO SHOW YOU, FIRST

LOCALIZED AND RELATED

SYSTEMICALLY.

AND HOW IMPORTANT THIS, IS

DRIVING THE PART OF THE

RESEARCH, HOW IMPORTANT THESE

ARE, HOW DIFFERENT THEY ARE TO

OTHER PROTEINS AND THE TYPE OF

KNOWLEDGE WE CAN GAIN OUT OF

THAT--OUT OF THIS MOLECULES.

WHY INSECT VS THIS TYPE¨<i OF

MOLECULES IN THE SALIVA.

WELL, ANYTIME ANY ARTHROPODS

ATTEMPTS TO GET A MEAL, THEY

CAUSE INJURY.

AND 1 OF THE FIRST SYSTEMS TO

COUNTERACT THIS IS THE

HEMOSTATIC SYSTEM, THEN IT'S

INTERESTING BIOCHEMICAL, WE DO

NOT WANT TO LOSE BLOOD.

WE IMMEDIATELY ACTIVATING THE

CONSTRICTION, AND BLOOD REG

LIEWLINGS TO PREVENT THE LOSS OF

BLOOD.

IF YOU PITCH YOURSELF WITH A

NEEDLE, YOU MAY HAVE BLOOD FOR A

FEW SECONDS AND THAT'S IT, IF A

MODEL

MOSQUITO, GETS YOU UNDER THE

SKIN IT WILL TAKE MINUTES AND IT

WILL BE HAPPILY LEACH AND LEAVE

FLYING.

AND THE COMPONENTS IN THE SALIVA

ARE ABLE TO BLOCK, CONSTRICTION

AND BLOOD CO AGULATION AND THIS

IS SOMETHING I DID FOR MANY

YEARS WHEN I WAS A DOCTORAL

STUDENTURAL STUDENT AND THEN

WHEN I MOVE LATER, WITH A FELLOW

HERE AT THE NIH WORKING WITH

THESE PROTEINS.

IN THE LAST FEW YEARS, WE HAVE

ENCOUNTERED NOT ONLY MANY

DIFFERENT--BUT NOT ONLY THE

MOLECULES THAT ARE IMPORTANT FOR

IRRIGATION, THAT OTHER TYPE OF

MOLECULES, VERY POTENT MOLECULES

AND THIS IS SOMETHING WE FOUND

IN THE LAST FEW YEARS, FOR

EXAMPLE, WE FOUND THAT WOB

PROTEIN FROM THE SALIVA, IT WAS

CALL LG111, IT'S AN IMPORTANT

INFLAMMATORY, IT INCREASES

NUTRIFILL ATTRACTION BY GSA, AND

MORE IMPORTANTLY, THIS MOLECULE

PREVENTS PAIN INDUCED BY

ARTHRITIS OR INHIBITS ARTHRITIS,

THIS IS AN ANTIART RITIC

MOLECULE.

THIS IS THE FIGURE, THIS IS THE

CONTROL AND INDUCED BY THE PAIN,

AND THIS IS IN COLLABORATION

WITH THIS GROUP IN BRAZIL, AND

MORE COLLEAGUES AND THIS IS JUST

A DEMONSTRATION--THIS IS FROM 30

TO 300 NANO GRAM, WITH VERY

SMALL AMOUNT, CAN YOU CHANGE NOT

ONLY THE PHARMACOLOGICAL EASTS

BUT ALSO INFLAMMATION.

THIS IS ANOTHER MOLECULE THAT WE

FOUND IN THE SALIVA AND IN THE

NUCLEUS, WHAT THEY WOULD DO IN

THE SALIVA OF SAND FLY, BUT WE

DISCOVER THIS THROUGH SEQUENCING

IN COLLABORATION WITHIEDY

COLBURN AND THE CAMPUS, THEY

DEMONSTRATE THAD

SALIVA--DEMONSTRATED THAT SALIVA

IS VERY QUICKLY DESTROYING THE

DNA.

NOW HOW DO WE CONNECT THIS IN

THE CONTEXT OF DISEASE?

AND THIS WAS CONNECTED BY--I WAS

TALKING TO DR. GOTTESMAN THIS,

IS INTERACTION OF SCIENTIST IN

AN OPEN BENCH ENVIRONMENT AT

NIH, THIS IS SOMETHING THAT I'VE

BEEN PRESENT [INDISCERNIBLE]

JUST TALKING TO PEOPLE AND THIS

IS IN COLLABORATION WITH A

DOCTORAL IN THE LAB, AND THEN

THEY ASK THE QUESTION, WELL,

THIS--THIS DNA IS SKIN DNA IN

THE NUTRIFILLS ARE IMPORTANT TO

PRODUCE NETS, THESE AREN'T JUST

DNA, AND THEY SHOWED THAT THIS

ACTUALLY CAN PRODUCE THIS NET,

CAN YOU SEE THE NETS HERE?

BUT IN THE PRESENCE EVER THESE

LGL138, THESE NETS ARE

COMPLETELY DESTROYED AND THEN

RIGHT IN THE SKIN, THE SKIN OF

THIS ANIMAL, OR THIS, BUT

IMAGINE THIS AND THE NUCLEACE,

DESTROYING NETS AND DESTROYING

THE NETS, ALLOWING THE PARASITE

AND GOING INTO THE NUTRIFILL

FILLS AND CAUSING EXACERBATION.

CAN YOU SEE HOW PARASITE TAKES

ADVANTAGE OF THIS MOLECULE AS

WELL.

TERMS OF ALL THE ASPECTS OF I'D

LIKE TO COVER THIS, IS THE

PHARMACOLOGY.

THIS EXAMPLE I SHOWED YOU IN THE

NUCLEACE, THIS CAN SHOW

[INDISCERNIBLE], THIS WAS

DEMONSTRATED MANY YEARS AGO BY

COLLEAGUES IN WHICH THEY CO

INJECTED SALIVA, OF SAND FLIES

WITH THIS MANY PARASITE, THIS

PREPARATION, PROMOTED INFECTION

AND IT WAS WAY DELETION WERE

BIGGER FOR IF YOU INJECT THIS

MANY ALONE, SHOWN THAT SALIVA

CAN MANUFACTURE THIS, AND THIS

WAS QUITE AN INTERESTING

FINDINGS, CALLED MY ATTENTION

FEW YEARS LATE SER THAT WE'RE

TRYING TO REPRODUCE THIS

EXPERIMENT AND THIS WAS IN

COLLABBUATION WITH JUSTIN AND

DAVID TUCKS LAB, AND WE IN THE

SALIVA MANY TIMES AND TO OUR

SURPRISE, THIS ANIMAL WERE

PROTECTED AND WE FIGURE OUT LATE

OR THAT IMMUNITY TO SAND FLY

SALIVA WAS PROTECTING ANIMALS

AGAINST THE INFECTION, AND THEN

WHAT I'M GOING TO TELL YOU NOW,

IS WHAT HAS BEEN OUR APPROACH IN

TRYING TO UNDERSTAND HOW THIS

PROCESS IS, HOW THE SALIVA CAN

PRODUCE--HOW THE SOPHISTICATED

LIVA CAN PROTECT AND WHAT ARTIST

MOLECULES, WHAT THIS CAN TELL

YOU ABOUT THIS PROCESS.

THEN WE TART JUST MANY YEARS

AGO, TO MORE PHARMACOLOGY,

BIOCHEMISTRY AND WE

TRANSITIONING TO THE APPROACH,

AND NOT ONLY GETTING DIFFERENT

EXPECT--BRINGING DIFFERENT

EXPECTATIONS IN THE LAB BUT ALSO

COLLABORATING WITH COLLEAGUES,

WITH DIFFERENT KNOWLEDGE, NOT

ONLY IN THE U.S. BUT ALSO AROUND

THE WORLD.

WE START DOING GENOMICS AND

INFORMATICS ABOUT TO UNDERSTAND

THIS HOST PARASITE INTERACTION

AND MOVING TO STATUS ASK

TOMMOLOGY, AND CLINICAL STUDY

WHICH I WILL NOT TALK MORE ABOUT

TODAY AND FINALLY THIS CLINICAL

STUDY.

THEN, THIS TO ME IS AN APPROACH

ALLOW US TO GO FROM MORE BENCH

BASIC STUDIES TO MORE CLINICAL

TRANSLATIONAL RESEARCH WHICH I

WILL WILL SHOW YOU IN A FEW

MINUTES.

THIS IS THE APPROACH TO SELECT

THE CLONES.

IT'S VERY SIMPLE APPROACH, WE

GET SAND FLIES

SALIVA--SALIVAIVEARY AND WE'RE

TALKING ABOUT 1999-2000 WHEN THE

FIRST PC R BASED LIBRARY CAME

OUT.

AT THAT TIME WE CALL MASSIVE CDA

SEQUENCING, WE'RE SEQUENCING 1

PLATE AND WE'RE SO EXCITED ABOUT

THIS GET 96 SEQUENCES AND THEN,

AT THE END, WE DID MUSCLE FIRST

WITH--AND WE DID MUSCLE FOR

SELECTION WITH 2000.

NOW THIS IS NOT MASSIVE--LIKE

SEQUENCES BUT REMEMBER, THIS

PROTEIN, THE NUMBER OF PROTEINS

IS LOW COMPLEXITY, THEN STILL

THIS TECHNIQUE IS APPLICABLE

TODAY.

THIS ALSO WAS A LEARNING

PROCESS, THIS CUSTOMIZED BY

INFORMATIC ANALYSIS, TO PREPARE

FOR US, FOR THE LAB AND IT'S

BEEN USED FOR MANY OTHER

SEQUENCES FROM

ARE--ADMINISTRATIVE THROUGH POD

AND HAS IMPACTED THE RESEARCH

AND VECTOR.

AND THE IDEA WAS TO SELECT WHAT

THE PROTEINS ARE SECLUDED FROM A

PERSON FLIES AND TEST IF THIS

PROTEIN PRODUCES THE IMMUNE

RESPONSE.

THIS IS JUST AN EXAMPLE OF

AGAIN, OF THE LO COMPLEXITY OF

THE PROTEINS YOU FIND IN THE

SALIVA OF SAND FLIES.

1 OF THE POINTS I WANT TO STRESS

WITH THE 35 SEQUENCES FROM THIS

IS THAT 50% OF THESE MOLECULES

ARE UNIQUE TO SAND FLIES.

YOU DON'T SEE IT IN OTHER

INSECTS OR ORGANISMS, IF YOU

CHECK IT, IF YOU'RE BLASTED TO

HUMAN GENOMES, DROSOPHILA

GENOMES, YOU WILL NOT SEE THIS

EXCLUSIVE TO SAND FLIES.

WE SHOULD--IT'S QUITE AN

INTERESTING--IF YOU THINK ABOUT

VACCINATION, I'LL COME BACK TO

THAT LATER.

WE GET ALL THESE PROTEINS AND

OUR NEXT STEP WAS HOW ARE WE

GOING TO USE--I WE WERE CUT OUT

OF THE LABS IN THE GENOMIC TIMES

BUT NOW OUR MISSION WAS HOW DO

WE SOLVE THIS PROBLEM?

WE HAVE ALL THESE SEQUENCES, HOW

ARE WE GOING TO STUDY THIS?

AND THIS WAS THE COINED MANY

YEARS AGO AND IT'S FUNCTIONAL

AND A LOT OF PEOPLE HAVE USED

FUNCTIONAL GENOMICS, AND TO ME

THE GENOMICS WAS A PARADIGM

SHIFT IN THE WAY WE DO RESEARCH

BUT IT'S ANOTHER CHIEF AGAIN IN

TERMS OF HOW WE CAN GO FOR

FUNCTIONAL DENATIONAL LIBRARY
OFGOMMICS WH
ICH IS

DOING GOOD BIOLOGY, GOODS

IMMUNOLOGY AND BIOCHEMISTRY WITH

THE SPECIFIC EVENT AND THIS IS

WHERE WE'RE TRYING TO GO.

AND HELP WITH OTHER GROUPS.

AND 1--SOMETHING WE DID THAT

TOOK US A LONG TIME WAS TO

PRODUCE RECOMBIN ANT PROTEINS

FIRST, WE TRY ON DIFFERENT

PLATPLATFORMS AND WE FAILED,

EITHER BY [INDISCERNIBLE] OR

BACKGROUND AND WE END UP WITH

RECOMBINANT PROTEINS IN THE

SYSTEM, AND VERY FEW PROTEIN WE

CAN GET AND ACTIVE AND SOLUBLE.

AND 1 OF THE BI-PRODUCTS, WE

SHOWED THAT YOU SALIVA CAN

PRODUCE AN IMMUNE RESPONSE IN

ANIMALS AND SOMETHING I LIKE TO

TAKE AS A BI-PRODUCT FOR

RESEARCH IS WE FOUND MOLECULES

THAT CAN WORK AS BIOMARKERS OR

MARKERS OF EXPOSURE AND THIS CAN

HELP ULTIMATELY THE

EPIDEMIOLOGICAL STUDIES ABOUT

LEISHMANIASES AND THEN PEOPLE

THAT ARE PRODUCING ASPECT BODIES

AGAINST THESE INSECTS MAY BE AT

HIGHER RISK OF CONTRACTING THE

DISEASE AND THEN CAN YOU DO THIS

STUDY.

AND WE GOT 2 MOLECULES, TO THE

PROTEINS, LGM17 AND LGM11 THAT

WE PRODUCE IN THE MAMMALIAN

CELLS AND WE DEMONSTRATE INDEED

LAB CONDITION THAT THEY WERE

VERY GOOD MARKERS OF EXPOSURE IN

HUMANS.

THIS PROTEINS WERE TEST INDEED

FIELD CONDITIONS--TESTED IN

FIELD CONDITIONS IN LARGER SCALE

AND THIS IS WITH COLLABORATORS

IN [INDISCERNIBLE] AND WE SHOW

WHEN YOU TEST 1 PROTEIN, THE

RESPONSE IS OKAY, EITHER 17 OR

11.

HOWEVER, YOU MIX THE 2, YOU HAD

VERY GOOD COVER.

WE SHOOT THEM STRAIGHT, AND WHEN

YOU COMPARE IT TO JUST THE WHOLE

SAN FRANCISCO LIVE ATHESE 2

PROTEINS ALLOW SUFFICIENT FOR

THE PROTECTION OF THE RESPONSE

IN THIS POPULATION.

THIS LGM17 AND LGM11 ARE GOOD

MARKERS, AND THEY'RE VERY

SPECIFIC FOR THE SAND FLY IN

THIS NEUROSEQUENCE REACTION,

WITH THESE MOSQUITOESER OTHER

PROTEINS, IT'S QUITE GOOD

MARKERS.

THIS IDEA OF THE MARKERS NOW HAS

BEEN TAKEN BY OTHER VECTOR BONE

DISEASES INCLUDING MALARIA FOR

MOSQUITOES IN AFRICK AAND ALSO

FOR AMERICA FOR [INDISCERNIBLE].

STILL FOR SAND FLIES WE STARTED

GETTING A LOT OF COLLABORATIONS

AND THEN, BECAUSE OF OF THIS

TIME, WE HAVE ALL THESE SAPPED

FLIES FINISHED WITH THE SMALL

NUMBERS OF 2 OR 3000, WE COVER

MOST OF THE IMPORTANT SAND FLIES

IN THE MIDDLE EAST IN NORTH

AFRICK AEUROPE, MEXICO AND SOME

IN CENTRAL AMERICA AND IN

BRAZIL.

WE STILL NEED TO COVER MORE OF

THE UPPER PART OF SOUTH AMERICA

AND OF COURSE, THE U.S. BUT AT

THIS POINT, WE HAVE DEVELOPED

THIS TECHNOLOGY AND THIS

APPROACH TO UNDERSTAND MORE OF

THE SALIVA--SALIVA AFRONsARY

AND THIS WILL BE USED OF THIS

PROTEINS WILL BE USED BY

DIFFERENT GROUPS AS AN EXAMPLE

OF MARKERS OF EXPOSURE FOR THE

STUDIES IN THOSE POPULATION.

ABOUT FOR VACCINES.

OUR OOH PROACH FOR THOSE

VACCINES, WE CALL THIS MOVIE

FROM THE THRUST TO THE IMMUNE

OHM, WE REALIZE IT WAS VERY

DIFFICULT TO GO TO IDENTIFY

THOSE PROTEINS AND GET ALL THE

RECOMBINANT PROTEINS FOR ALL OF

THEM AT ONCE.

WE DECIDED TO DO A HIGH THROUGH

PUT CLONE NOTHING THE DNA

PLASMID THAT HAS A SINGLE

PEPTIDE THAT WILL ALLOW THE

PROTEIN TO BE--WHEN WE INJECT

THE DNA TO BE SECRETED AND

PRESENT IT TOED ANTIGEN GEL, THE

SAME WAY WHEN IT INSCWECTED BY

THE INSECT.

THEN WE TEST FOR A RESPONSE AND

ANTIBODY RESPONSE AND THEN JUST

TO MAKE IT PRETTY SHORT, FROM

THE DIFFERENT TRANSCRIPT OHMS

THAT WE TESTED, ABOUT 20% OF THE

PROTEINS PRODUCED HAVE BPh

RESPONSE AND THEN WE TESTED

THOSE PROTEINS, CAN THESE

MOLECULES THAT PRODUS A FILLER

RESPONSE, PROTECT AGAINST

LEISHMANIASES.

AND THE ANSWER IS YES, AND IT'S

YES FOR THE 2 SYSTEMS.

WE TESTED A MOLECULE, CALLED BPS

15 IT'S A NOVEL PROTEIN, NOT

SIMILAR TO OTHER PROTEINS IN

BANK, ANIMALS THAT WERE

VACINATED WITH SP15, WERE

PROTECTED WITH BLACK 6 AND

ANIMALS WERE IMMUNIZE WIDE

CONTROL DNA AND IMMUNITY TO AN

ISOLATED DNA VACCINE CAN PROTECT

MICE AGAINST LEISHMANIASES AND

THEN WE DID A MUCH STRONGER PART

OR PARSIGHT WHICH IS

LEISHMANIASES AND THIS IS IN

COLLABORATION WITH--IT WAS DONE

BY REGGIE GOURM AN AND IN

COLLABORATION ALSO WITH CLYDE

[INDISCERNIBLE] IN BRAZIL.

HERE WE DEMONSTRATED THAT

HAMSTERS THAT WERE VACINATE WIDE

CONTROL DNA AND THEN CHALLENGED

WITH HUNDRED THOUSAND PARASITE

IN THE SALIVA, ALL THESE

HAMSTERS OVER A PERIOD OF TIME

JUST DIE, ALL HAMSTERS VACINATE

WIDE ANOTHER NOVEL MOLECULE FROM

[INDISCERNIBLE] THE PULP IS

NAMED LG19, SURVIVED THE

POWERFUL CHALLENGE OF

[INDISCERNIBLE], THE FORM.

THIS EXPERIMENT AND THIS DATA

HAS BEEN REPRODUCED AND

PUBLISHED A COUPLE MONTHS AGO BY

ANOTHER INVESTIGATOR IN BRAZIL.

ANOTHER GROUP OF ANOTHER

RESEARCHERS AND THIS FIND IS

QUITE REPRODUCIBLE AND THESE CAN

PREVENT B-CELL MANAGEMENT.

MOSTLY, THE DATA I SHOWED YOU,

THE EXPERIMENTS WE HAVE DONE,

HAVE BEEN USING NEEDLE AS A

CHALLENGE.

WE VACINATE THE ANIMALS WITH THE

VACCINE AND THEN THEY CHALLENGE

THEM WITH A SYRINGE WITH THE

NEEDLE, WITH THE SALIVA.

IN SAVE EDUCATIONAL'S LAB SHOW A

COUPLE OF YEARS AGO, SHOW THE

TRANSMISSION OF LEASH MANIA THAT

IF ANIMALS THAT ARE PROTECTED

AGAINST NEEDLE, WHEN THEY'RE

VACINATED WITH THE X-VACCINE,

THEY ARE NOT PROTECTED WHEN

THEY'RE CHALLENGED WITH AN

INFECTED SAME FLIGHT, BY.

THEN OUR QUESTION WAS AND WE

KNOW, WE'LL SHOW YOU ALL THE

MOLECULES THAT ARE PRESENT IN

THE SALIVA OF THIS INSECT.

I WILL SHOW YOU HOW POWERFUL

THIS MOLECULES CAN MODIFY NOT

ONLY THE HEMOSTASIS BUT ALSO

INFLAMMATION AND RESPONSES AND

THEN WE ASK THE QUESTION, CAN

THESE MOLECULES THAT WE HAVE

BEEN TESTED BY NEEDLE, CAN THEY

PROTECT AGAINST THE CHALLENGE OF

AN INFECTED FLY?

FOR THIS WE USE 1 MOLECULE THAT

IS CALLED LGM THAT WE HAVE

TESTED AS A DNA PLASMID AND

PROTECTED WITH NEEDLE AND WE

PROBABLY SHOULD HAVE THAT A

COUPLE OF MONTHS AGO AND THIS IS

SOMETHING I WANT TO STRESS HERE,

SOMETHING THAT IS VERY

IMPORTANT, SOMETHING THAT I LIKE

TO HAVE SOME FEEDBACK IN CASE

SOMEBODY KNOWS THIS ANSWER.

WE INJECTED LGM 11, OHM 500 NANO

GRAMS OF THIS PROTEIN VERSES THE

SHORTER MICROGRAMS, TONS OF

MICROGRAMS, AND NO ADJUVANT.

500 NANO GRAMS WITH NO ADJUVANT.

I'VE BEEN GOING TO DIFFERENT

VACNOLOGY MEETING IN THE LAST

YEAR AND ASKED THE QUESTION: 

CAN YOU TELL ME IF YOU HAVE

TESTED A VACCINE WITH ONLY 500

NANO GRAM IN THE ABSENCE OF AN

ADJUVANT THAT CAN PRODUCE A

STRONG AND LASTING IMMUNE

RESPONSE AND SO FAR THE ANSWER

IS NO.

THEY HAVE TEST WIDE WHOLE

PARASITES OR OTHERS, BUT NOT

WITH A SINGLE PROTEIN.

THEN THAT'S SOMETHING THAT I

LIKE TO STRESS HERE.

THIS PROTEIN WITH NO ADJUVANT

AND A SMALL AMOUNT, WE TESTED

FIRST TO SEE IF THERE'S A

RESPONSE TO UNDERSTAND IMMUNITY

OF THIS PROTEIN AND LATER WE

CHALLENGE THEM WITH INFECTED

SAND FLIES.

WE WANT TO KNOW IF THIS PROTEIN,

IMMUNITY INDUCED BY THE PROTEIN

IS STRONG ENOUGH TO CONTROL, TO

PREVENT LEISHMANIASES OR

ESTABLISHMENT OFLISH MANIA WHEN

IT'S INFECTED BY THE SAND FLY

THE NATURAL ROUTE.

WE DEMONSTRATED THAT WHEN YOU

TEST THIS ANIMAL BEFORE THE

CHALLENGE AND YOU GET

STIMULATE--YOU GET THE DENDRITIC

CELLS TOGETHER WITH THE LGM 11

AND YOU STIMULATE LYMPHNODE

CELLS WITH THE VACINATED ANIMAL,

THAT PRODUCE GOOD LEVELS OF

INTERFERON-GAMMA BUT NOT IN THE

NAIVE, OR NOT WHEN THEY'RE NOT

PRODUCED OR NOT WHEN THE DISEASE

NOT IN CONTACT WITH LGM11 AND

SAME WAS FOR IL10 AND UP HERE

THERE IS NO PRODO YOU RECOGNIZE

OF IL4 WHICH IS THE TH2 CYTOKINE

THAT IS KNOWN TO ACTUALLY

PROMOTE LEISHMANIASES.

THIS DATA INDICATES A SPECIFIC

TH 1 TYPE IMMUNITY TO THIS

PROBLEM.

AND AGAIN THIS IS ACHIEVE WIDE

ONLY 500 NANO GRAMS.

IN THE ABSENT--[INDISCERNIBLE].

WHAT HAPPENED TO THESE LG11

ANIMALS WHEN THEY'RE CHALLENGED

WITH INFECTED FLYS AND WHAT WE

SAID HERE IS THAT ANIMALS SHOWN

HERE AS A PICTURE FIRST CONTROLS

VERY LTHE PATHOLOGY.

THERE IS NO PATHOLOGY IN THIS

ANIMAL.

THERE IS NO LIESHMANNIA

INFECTION AND THIS IS OLDSMOBILE

2 WEEKS POST CHALLENGE AND ALSO

THE NUMBER OF PARASITES IN THE

LYMPHNODE OF THE EAR ARE

DECREASING SIGNIFICANTLY.

1 OF THE THINGS THAT CALL THIS

ATTENTION, 2 WEEKS AFTER

CHALLENGE IS FIRST FYOU

STIMULATE WITH LGM 11 WE EXPECT

TO SEE A RESPONSE, WE SAW BEFORE

IN THE CHALLENGE, TH1 TYPE OF

INTERFERON-GAMMA IN ANIMALS THAT

WE'RE VACINATE WIDE LGM 11 AND

WE STIMULATE THE CELLS, AND YOU

SEE INTERFERON-GAMMA HOWEVER, IF

YOU STIMULATE THESE ANIMALS WITH

LEASH MANIA AND YOU SEE THE

PARAMETERS OF THEM AT THIS TIME,

WE SEE THAT BSA VACINATED

ANIMALS HAVE LOTS OF

INTERFERON-GAMMA BUT NOT THE LGM

11.

THIS MAY BE PROBABLY DUE TO THE

SMALL NUMBER OF PARASITE BUT WE

HYPOTH SIZE THAT THE IMUGITY TO

THIS PROTEIN IS REGULATING, NOT

ONLY THE PERSONS OR THE PARASITE

BUT HOW THE HOST RESPONDS TO THE

PARASITE.

THAT'S WHY WE DON'T SEE THESE

LESIONS, THIS PATHOLOGY.

MORE ABOUT THE MECHANISM OF THE

LGM11 AND WE WANT TO KNOW THE

CONTRIBUTION OF BCL ANTIBODY, IS

THIS PROTEIN MAKING ANTIBODIES

AND THEN THEY'RE NEUTRALIZING

THE EFFECT OF LNKS GM11 AND THE

ANSWER TO THAT IS NO.

BECAUSE WHEN WE HAVE--WHEN WE

IMMUNIZE LGM 11 AND B-CELL

DEFICIENT MICE, WE DON'T SEE--WE

DON'T SEE ANTIBODIES TO BE

LGM11.

WE SEE A GOOD CELL RESPONSIBLE

AS A FORM, AND THEY'RE CHALLENGE

WIDE BITES AND HOWEVER, ANIMALS

THAT WERE CHALLENGED WITH THE

INFECTED SAND FLIES, THEY STILL

PROTECT.

IT'S VERY STRONG ROUGH ATOM

PROTECTION THAN B-CELLS,

ANTIBODIES ARE NOT MAKING ANY

DIFFERENT, THEY'RE NOT IMPORTANT

FOR PROTECTION WHEN USING LGM

11.

HOW ABOUT CD14 CELLS.

CD14 CELLS ARE [INDISCERNIBLE]

GOING TO THE TERMINAL FOR THE

CELLULAR RESPONSES ARE

IMPORTANT, WE DELETED THE CD14

CELLS FROM THESE ANIMALS 48

HOURS BEFORE AND THEN EVERY WEEK

AFTER THE CHALLENGE.

AND WHAT WE OBSERVE HERE IS THAT

ANIMALS THAT ARE ARE DEPLETED

LG11 ANIMALS DEPLETED WITH CD4,

LOST THE ABILITY TO CONTROL

LEISHMANIASES INFECTION, THIS

INDICATED AGAIN THAT THESE ARE

IMPORTANT FOR PROTECTION INDUCED

BY LGM 11 AGAINST LEISHMANIA,

ANOTHER ASTHMAPOLIS SPECT

OF--ASPECT OF VACCINATION IS HOW

LONG IT CAN LAST?

AND PARTICULARLY AGAIN,

EMPHASIZING, NO ADJUVANT AND

ONLY 500 NANO GRAMS IN IN

ANIMALS.

GRADUATED 5 MONTHS AFTER THE

LAST VACCINATION, CHALLENGE THIS

ANIMALS AGAIN WITH INFECTED SAND

FLYS AND THIS ANIMAL AGAIN WERE

ABLE TO CONTROL THIS INFECTION

COMPARED TO THE CONTROL GROUP.

AND AGAIN, SMALL NUMBERS OF

PARASITE, THIS IS NOT STERILE

IMMUNITY, BUT THERE'S NO

PATHOLOGY.

NO PATHOLOGY IN THE ANIMALS,

LOOK AT THE LESION SIZE,

LOOK--AND AGAIN, WE BELIEVE THAT

THIS HYPOTHESIZE, THAT THIS

PROTEIN IS REGULATING HOW THE

HOUSE IS RESPONDING TO THE

PARASIGHT, BUT IS IT ONLY

REGULATION TO THE PARASITE WAS

ACTUALLY, WE DON'T BELIEVE SO,

THESE ANIMALS OR THESE PROTEIN

IS ACTUALLY DOING GOOD THINGS,

THE FIRST SIGHT I SHOWED YOU 2

WEEKS MAY BE REGULATING A

RESPONSE BUT LATER ON WHEN WE

CHECK IT AT 5 WEEKS AND IF WE

STIMULATE CELLS AGAIN WITH SLA

CELLS COMING FROM LGM 11 OR BSA

IN THE NEXT MICE, WE SEE MORE

CD4 T-CELLS PRODUCING

INTERFERON-GAMMA IN THE

LG-VACINATED MICE AND THIS IS

IMMUNITY TO THE PARASITE.

WITH THE CONTROL BSA, SUGGESTING

THAT EITHER THERE IS A DELAY IN

THIS--IN THE IMMUNITY, IT WAS A

SWITCH OF MORE EFFECTOR OF THIS

PROTEIN, BUT, WHILE WE'RE

HEADING RIGHT NOW, WITH PROTEIN

WITH SMALL AMOUNT OF--REMOVE

THE--CAN INDUCE THE TH1 TYPE

IMMUNITY THAT CAN PROTECT THE

ANIMALS AND CAN CONFIRM

ANTILEISHMANNIA IMMUNITY THEN WE

GO FROM ANTIIMMUNITY TO A

PROTECTIVE AND PROPER--EMPHASIZE

THE PROPER, WE NEED TO

UNDERSTAND MORE HOW PROPER AND

EFFECTIVE ANTILEISHMANNIA

IMMUNITY.

WHAT IS LJ11, IT'S A RELATED

PROTEIN.

YOU FIND IT IN OTHER INSECTS BUT

NOT IN SALIVA, FOUND ONLY IN

SALIVA OF SAND FLIES.

JOHN ANDERSON, DEMONSTRATED THE

KRYSTAL STRUCTURE AND ALSO

DEMONSTRATE THAD THIS PROTEIN IS

THE SEROTONIN BINDING PROPERTY.

SO BY SER ON TONEIN

[INDISCERNIBLE] THERE'S ANOTHER

PHARMACOLOGICALLY ACTIVE

COMPONENT IN THE SALIVA.

BUT WE ALSO WANT TO KNOW IF THIS

SER ON TONEIN BINDING PROPERTY

HAS TO DO WITH PROTECTION AND

ACTUALLY, THE ANSWER IS NO

BECAUSE WE HAVE ANOTHER

SALIVA--SALIVAIVEARY PROTEIN,

CALLED LJM111 WHICH I SHOW YOU

THE BEGINNING OF THE TALK IT WAS

AN ANTITRIED MOLECULE, BOTH OF

THESE MOLECULES, BIND SEROTONIN.

THIS MOLECULE PRODUCE TH1 TYPE

PROTECTIVE, THIS 1 DOESN'T.

THE ONLY DIFFERENT WEAN THE LGM

11 WITH KHI IS IMMUNOGENIC AND

PROTECTIVE AND THE 111 WHICH IS

IMMUNOGENIC WHICH IS IN THE FACE

OF THE PRACTICES TEEN.

IT'S A CHARGE, IT HAS A CHARGE,

PARTICULAR CHARGE FACE IN THAT

TITLE OF PROTEIN.

YOU DON'T SEE THAT IN THE

LGM111.

YOU DON'T SEE THAT, YOU SEE

ONLY--IF YOU GO TO THE--IF WE GO

G TO PRIMARY SEQUENCE, YOU DON'T

NOTICE THAT.

IT'S VERY DIFFICULT TO SEE THAT.

YOU HAVE TO DISTRIBUTE THE LOWER

MOLECULE, BUT ONLY WHEN THE

KRYSTAL LIKE STRUCTURE WAS SOLD,

THEY APPOINTED OUT THAT THIS WAS

QUITE A DIFFERENT AND QUITE

UNIQUE, THEN WE HYPOTHESIZED

THAT PROBABLY DISCHARGE IT IS

THE 1 THAT IS MAKE THANKSGIVING

MOLECULE UNIQUE.

IN TERMS OF PRODUCING THIS TYPE

OF CELLULAR IMMUNE RESPONSE,

CONFIRM THAT LONG-TERM

PROTECTION, AND WE STILL DO NOT

KNOW ABOUT INNATE IMMUNITY AND

THIS IS SOMETHING WE ARE

INVESTIGATING RIGHT NOW.

HOW THIS PROTEIN CAN PRIME THE

IMMUNE SYSTEM?

LATE OR CONFIRM AT TH1 TYPE

LONG-TERM PROTECTION, WITH AN

ADJUVANT.

WHICH SOMETIMES WE CALL THIS

PROTEIN, NONCLASSICAL ADJUVANT.

BECAUSE--ADJUVANTS IN GENERAL

CANNOT PRODUCE AN IMMUNE

RESPONSE, AND THIS 1 IS

PRODUCING AN IMMUNE RESPONSE

ITSELF BUT IT'S DOING SOMETHING

THE ADJUVANTS DO WHICH IS

BRIDGING THEMSELVES AND CHANGES

THE ENVIRONMENT.

THEN THIS IS QUITE A UNIQUE

PROTEIN IN THAT SENSE.

I WAS VERY EXCITED ABOUT THIS

PROTEIN AND TRY TO UNDERSTAND

THE MECHANISM BUT WE WANTED TO

KNOW, CAN WE TRANSLATE THIS

INFORMATION TO LARGER ANIMAL

SYMPATHETIC NERVOUS SYSTEM I

MEAN THIS IS--LARGER ANIMALS?

THIS IS A PHENOMENON OR IT ONLY

HAPPENS IN BLACK 6 OR HAPPENS IN

AN ORGANISM OF [INDISCERNIBLE].

AND THEN A COLLEAGUE ASKED THE

QUESTION, VERY SIMPLE QUESTION: 

CAN MONKEYS, CAN RECESS MONKEYS

GET IT FROM THE BITE?

AND THE ANSWER IS YES, WE HAVE

20 INFECTED [INDISCERNIBLE]

EVERY 21 DAYS AND THEY PRODUCE

VERY TYPICAL INFLITERATION AND

SKIN REACTION AND THE SKIN OF

THESE ANIMALS AND THE SAME PC R

BUT IT'S LOTS OF

INTERFERON-GAMMA IN THE SKIN OF

THIS ANIMAL AND THE QUESTION WAS

VERY OBVIOUS:  CAN MONKEYS THAT

HAVE BEEN EXPOSED TO BITE AND

THEN PRODUCE AN IMMUNE RESPONSE

BE CHALLENGE WITH INFECTED BITES

WOULD THEY BE PROTECTED AGAINST

LEISHMANIASES INFECTION AND THE

ANSWER IS YES?

ONE ANIMAL WE ARE REPEATING THE

WHOLE GROUP AGAIN BUT JUST TO

HEAR NAIVE ANIMALS, THIS IS 9

WEEKS AFTER INFECTION, YOU SEE

LOTS OF MISSIONS VERSES EXPOSED

GROUP THAT HAS MADE LINER

LESIONS, WE ALSO IDENTIFY, THIS

IS--THIS WAS REPEATED A COUPLE

OF TIMES BUT THE 1 WHO IDENTIFY

1 MOLECULE FROM THE SALIVA, THE

SAND FLY THAT IS ABLE TO PROTECT

MONKEYS BUT WE DID ONLY--ONLY

ONCE WE'RE REPEATING THAT

EXPERIMENT IN THE NEXT FEW

MONTHS.

>> WE'LL BE MOVING MORE FOR THE

STUDIES IN THE MOUSE MODELS,

WE'LL GO INTO LARGER ANIMAL

MODELS, WE UNDERTOOK WITH THE

CRATE AND DOING VACCINES FOR

DOGGINGS.

DOGS ARE LEISHMANIASES BUT I CAN

TELL YOU IT'S WORKING DOGS, AND

WE HAVE A COLLABORATION WITH

THIS COMPANY.

IN BRAZIL, WE'RE FOLLOWING THE

SAME APPROACH.

BUT FOR OUR CLINICAL STUDIES WE

WANT TO KNOW MORE ABOUT HUMANS,

I MEAN HOW RESPOND TO SALIVA,

HOW HUMANS RESPOND TO SALIVA,

NUMBER 1 IN FIELD CONDITIONS, I

HAD TO MAKE A POLICY BECAUSE I

THINK SOMEBODY'S GOING TO ASK ME

THIS QUESTION AT THE END ANYWAY

BECAUSE WE'VE BEEN ASKING THIS

QUESTION, MANY TIMES.

OKAY, IF SALIVA IMMUNITY

PROTECTS, HOW COME THERE'S

PEOPLE WITH LEISHMANIASES IN THE

FIELD?

GOOD QUESTION.

WELL, IF SALIVA IS--LIKE

MOSQUITOES PRODUCE IMMUNE

RESPONSE, YOU MAY LOSE THAT

ABILITY PRODUCE SIMILAR RESPONSE

OR IMMUNITY TO THESE AFTER MANY

BITES, VERY VALID QUESTION AND I

THINK THAT'S--IT MOVES MORE INTO

THE FIELD, TO UNDERSTAND REAL

SITUATIONS.

WE HAVE 2 STUDIES, 1 IN FIELD

CONDITIONS IN MALI, THIS IS

DR. WATTS, WHICH INSPIRES FORCES

TO GO TO MALI.

HE SAID THERE IS GREAT

OPPORTUNITY AT THAT TIME, WE'RE

TALKING ABOUT 2002, 2003, I

DIDN'T UNDERSTAND ALL THE

LOGISTICS IN THE PROCESS BUT I

THINK IT WAS 1 OF THE--FOR ME

GOING INTO THAT AREA AND DO

THANKSGIVING RESEARCH IT'S BEEN

1 OF THE MOST REWARDING

EXPERIENCES, NOT ONLY IN THE

SENSE OF THE SIGNS BUT ALSO TO

SEE THE DISEASE IN THE AREA, TO

SEE THE PEOPLE THAT ARE--THAT

CAN PARTICIPATE, THAT

[INDISCERNIBLE] OF THIS

EXPERIENCE AND I'M REALLY

FORTUNATE TO HAVE EXPERIENCED

THIS.

AND THEN WE SELECT THE VILLAGE

IN MALI, WHICH IS ABOUT--MANY

HOURS I DON'T REMEMBER THE

HOURS, IT LOOKS FOREVER WHEN YOU

DRIVE FROM BAMAKA, TO THE AREA

[INDISCERNIBLE].

AND THIS VILLAGE IS ABOUT 1600

INDIVIDUALS WITHIN THE 2.

WE ALSO DIDDENT O MODEL CITIZEN

LOGICAL STUDIES THERE, AND

[INDISCERNIBLE] HAS A VECTOR AND

WE FOUND MANY OTHER SAND FLYS

AND BUT THIS IS THE MAIN VECTOR

THERE, WHICH MAKES THE STUDY

MUCH SIMPLER IN THAT AREA.

WE ASK THE QUESTION:  CAN PEOPLE

PRODUCE IMMUNE RESPONSES TO THE

SALIVA?

AND I DON'T HAVE--THERE WAS SOME

BLOOD HERE, BUT YES, ANTIBODIES

THEY HAVE.

AND I THINK THAT'S' A GIVEN, BUT

HOW ABOUT CELLULAR IMMUNE

RESPONSES IN CAN PEOPLE LIVE IN

THESE AREA WITH IMMUNE RESPONSES

AND WE'RE TALKING ABOUT PEOPLE

WHO HAVE LIVED THYROID CARCINOMA

FOR MANY YEARS AND THIS STUDY

WENT--THIS IS FROM ADULTS 18 TO

65 AND THE ANSWER IS YES, IF YOU

THINK THE PBMCs OF THE

INDIVIDUAL, [INDISCERNIBLE] AND

STIMULATE WITH THE

SALIVA--SALIVAIVEARY----SAN

FRANCISCO„i LIVEARY

GLAND--SALIVERY GLAND,

[INDISCERNIBLE] IL13, 14, AND 5,

THIS IS RESPONSE TO ANYTHING BUT

MUST HAVE BEEN RESPONSE TO

SOMETHING.

BUT STILL, THAT DOESN'T ANSWER

THE QUESTION OF WHY IF THERE IS,

IF THEY'RE BITTEN, WHY WE

BELIEVE THAT SALIVA WILL

HYPOTHESIZE THAT SAN FRANCISCO

LIVA IS

IMPORTANT--SALIVA--SALIVA I'VEA

 IMPORTANT FOR PROTECTION, WHY

THE INDIVIDUAL HAS THE DISEASE?

WELL WE FOUND SOMETHING

INTERESTING WITHIN THIS GROUP.

WE FOUND A SUBGROUP OF THAT WE

CALL TH1 RESPONDERS, AND TH2

RESPONDERS TO SALIVA, WE WE

FOUND SOME INDIVIDUALS CAN

PRODUCE TO THE SALIVA OF

[INDISCERNIBLE], HIGH LEVELS OF

INTERFERON-GAMMA AND IL12 AND

MUCH LOWER OF I L5 AND 13.

ANOTHER GROUP, IT H2, RESPONDERS

IS MUCH LESS INTERFERON-GAMMA

BUT MUCH HIGHER IL5 AND 13, AND

OF COURSE WE HAD THE THIRD GROUP

WHICH IS THE NONRESPONDERS.

IT'S A GROUP.

BUT JUST TO NOT RESPOND.

THEN YOU THINK ABOUT TWE'RE

PROPOSING THAT PROBABLY, WHY IN

AN ENDEMIC AREA, EVEN IF YOU

HAVE IMMUNITY TO SALIVA, YOU

STILL MAY NOT BE PROTECTED, WE

HYPOTH SCIZZED THAT EVEN YOU ARE

NOT RESPONDER OR YOU'RE A TH2

LIKE RESPONDER TO THE HOST

SALIVA AND MAYBE THERE ARE

RESPONDERS THAT ARE DOSE 1 THAT

ARE PROTECTED.

WE'RE STILL--WE'RE DO

THANKSGIVING ANALYSIS--DOING

THIS ANALYSIS TO CLARIFY THIS

QUESTION, BUT AT LEAST WE HAVE

SOMETHING NEW OR A NEW

HYPOTHESIS TO ANSWER THIS

QUESTION THAT WE HAVE ALWAYS

BEEN ASKED.

HOW ABOUT THE SECOND POINT THAT

I TOLD YOU.

IF YOU'VE BEATEN MANY TIMES YOU

CAN STILL MOUNT A CELLULAR

IMMUNE RESPONSE TO THE SALIVA OF

THIS INSECT?

AND WE ASK THAT QUESTION IN

MALI.„i

, WE SELECTED INDIVIDUALS, I

THINK IT'S MUCH LOWER, 5-65 AND

THIS IS A VERY FUNNY STORY.

THE COLONY WE HAVE HERE AT NIH,

EVEN IN THE LAB, IS COMING FROM

THE [INDISCERNIBLE], WE GOT

FLIES FROM THERE TO HELP US DO

THAT.

WE COLONIZE THE FLYS AND THEN WE

WANT TO DO THIS ANALYSIS BUT WE

COULDN'T USE THE FLIES FROM MALI

BECAUSE THEY'RE WILD CARDS AND

THEY HAVE LEISHMANIASES, THEY

HAVE TO GET THE FLIES FROM HERE

BACK TO MALI, WHICH MEANS

THEY'RE GOING TO SEE THEIR

RELATIVES.

[LAUGHTER]

BUT ALSO, TO US IT'S VERY

IMPORTANT BECAUSE WHEN PEOPLE

ARE BITTEN BY NATURAL FLIES

WOULD REACT TO FLIES THAT ARE

COLON EYES.

--COLOONIZED.

THERE WAS QUITE IMPORTANT TO

ANSWER THIS QUESTION, WELL WE

TOOK THE FLYS AND WE ONLY EXPOSE

THIS INDIVIDUAL, TO TREATED FLY

IT

FLY--FLYS AND THIS WAS THE SIGN

IN THE LAB AND THE FLIES ARE

CONTAINED AND THE ADVANTAGE IS

YOU CAN SEE IT'S A PLEXIGLASS,

CAN YOU SEE THE FLIES ARE FED.

THEY'RE VERY RED.

AND THEN YOU ADD IT TO YOUR ARM

AND WAIT OHM A FEW MINUTES, I

THINK 10 TO 20 MINUTES AND

THEY--THE IS WHAT WE SEE.

WE SEE THAT MINUTES AFTER BITES

YOU DON'T SEE MUCH OF A RESPONSE

IN SOME INDIVIDUALS, ALTHOUGH

SOME INDIVIDUALS, THEY DO; THEY

HAVE MORE IMMEDIATE RESPONSE,

PARTICULARLY KIDS AND IT'S

SOMETHING WE'RE TRYING TO

INVESTIGATE MORE BUT 48 HOURS

AFTER THE BITE, WE SEE A TYPICAL

BPh.

THAT IF YOU TAKE A BIOPSY, YOU

SEE THE CELL RECRUITMENT IN THE

SIDE.

THE BOTTOM LINE IS THAT ABOUT

65% OF INDIVIDUALS FROM THIS

AREA RESPONDED TO THE BITES OF

THE FLIES WHICH MEANS THEY DID

NOT LOSE THE ABILITY TO RESPOND.

EVEN AFTER ALL THESE YEARS.

THIS IS SOMETHING THAT I LIKE TO

EMPHASIZE HERE.

SAND FLIES ARE NOT MOSQUITOES.

OKAY?

EVEN WHEN WE CHECK THE

TRANSCRIPT OHM OF THE FLIES

THERE ARE ONLY LIKE FEW PROTEINS

THAT ARE SIMILAR TO MODEL

CITIZEN MOSQUITOES,

[INDISCERNIBLE] ARE MORE THAN

HUNDRED SOMETHING SEPARATED BUT

THEY COME TO [INDISCERNIBLE]

MORE INDEPENDENTLY, THEN

ALTHOUGH WE TREAT THEM LIKE

EQUAL, BECAUSE THEY SUCK BLOOD,

AND MAY MAKE AN ITCHY RESPONSE,

THEY'RE NOT THE SAME.

SAND FLIES IN IN CASE ARE

TELLING US THAT THE WAY WE

RESPOND TO FLIGHT IS DIFFERENT

BECAUSE OF THE TYPE OF THE

RESPONSE TO Ph, AND ALSO WE

TEND TO MAINTAIN THE RESPONSE

FOR LONGER TIME, PROBABLY BY THE

TYPE AMOUNT AND TYPE OF PROTEIN

I INJECTED INTO THE HOST, AND

SOME OF THE INDIVIDUALS, IF YOU

TAKE THE FREQUENCY OF THE BPh

POSITIVE, YOU START SEEING THAT

THE MAJORITY OF PEOPLE DO NOT

LOSE THE RESPONSE, ALTHOUGH

AFTER 45 OR 50 YEARS, IT DROPS.

THERE IS A LOSS, BUT THE

MAGGORRITY BETWEEN AGE 41-45,

THEY MAIN ABILITY TO INDUCE Ph

RESPONSE TO SALIVA.

AND THIS IMMUNE RESPONSE IS

TYPICAL FOR BPh AND THIS IS IN

NUTRIFILLS AND MACK WOPHAGES

AND--MACROPHAGES AND THEN YOU

HAVE A MORE ALLERGIC RESPONSE

AND THIS APPEARS AGAIN TO BE CD4

MEDIATED.

IT WOULD TAKE A BIOPSY OF 1 OF

THESE REACTIVE SITES FROM 15

INDIVIDUALS WE SEE THIS REACTIVE

TYPE PRODUCING LOTS OF

INTERFERON-GAMMA AND EVEN AFTER

SO MANY YEARS OF EXPOSURE THAT

WILL BE DIFFERENT TO DETERMINE A

PARTICULAR AGE GROUP IN AN

INDEMMIC AREA, AND MANY PEOPLE

THAT ARE REACTIVE, THEY PRODUCE

A TH1 SALIVA, AND THAT MAKES

THIS CONNECTION AND THIS QUITE

AN INTERESTING.

THAT'S WHY I MENTION ABOUT IN

THE FIELD, THIS WILL GIVE YOU A

BETTER RESPONSE, THIS IS A

DISEASE AND WERE BITTEN BY THE

FLYS AND THIS IS WHAT WE'RE

LEARNING RIGHT NOW.

THAT WAS THE FIRST STUDY.

THAT WAS AN ENDEMIC AREA.

YOU CANNOT CONTROL THE NUMBER OF

FLIES, YOU THE NUMBER WHEN THEY

WERE ENCOUNTERED AND THE BITES

WERE HOW LONG, AND WE DID

ANOTHER STUDY IN HEALTHY

VOLUNTEERS.

THIS WAS AAWARDED BY THE NIH

CLINICAL CENTER, WE GOT A BENCH

TO BEDSIDE AWARD TO DO THIS

PROJECT.

AND THIS IS IN COLLABORATION

WITH WALTER REID WITH DR. AARON

SON AND THE QUESTION WAS THE

SAME, HOW HEALTHY VOLUNTEERS

WHEN EXPOSED TO BITE.

WHAT IS THE IMMUNE RESPONSE, HOW

CAN THEY REACT OVER TIME.

CAN THEY PRODUCE A TH1 TYPE

RESPONSE?

AND IN THIS SITUATION, WE'RE

UNDERSTANDING MORE, CAN WE

IDENTIFY MOLECULES, FROM THE

SALIVA OF SAND FLY BUT CAN'T

ROUGH ATOM PROCESSES DUCE A TH1

RESPONSES HUMANS DO THEY EXIST

AS A MOLECULE?

THEN?

THIS STUDIES ONGOING, THIS IS

HERE THIS, IS 9 MONTHS, I THINK

[INDISCERNIBLE], ALMOST OVER, 3

MORE MONTHS MONTHS AND WE FINISH
THE

PROJECT BUT AT LEAST, WE TAKE A

SNAPSHOT, WE SEE THAT MOST OF

THE INDIVIDUALS WHICH WE HAVE

ANTIBODIES, THEY PRODUCE ASPECT

BODIES EITHER THAT WE'RE EXPOSED

TO, AND THIS COLOR, ATTENTION,

THEY RESPOND DIFFERENTLY.

THE PEOPLE WITH THE--THEY MAKE

LESS ANTED BODIES AND ALSO THE

SAME WAS WITH THE FILLER IMMUNE

RESPONSE AND THEN EVEN WHEN

WE'RE COMPARING MOSQUITOES TO

THE DIFFERENT, WE'RE COMPARING

SAND FLIES, TO THE THE SAME

DIFFERENCE AND I CAN TELL YOU

THAT THERE'S SOME MOLECULES THAT

ARE UNIQUE THAT YOU DON'T FIND

IN THERE AND VICE VERSA AND THEN

IT'S NOT A SURPRISE, IF WE PUT

IN THE CONTEXT OF THE MOLECULES

THAT WE FIND THE TRANSCRIPT OHM.

THESE INDIVIDUALS WHEN YOU HAVE

THE PBMCASKS STIMULATE WITH

SALIVA EITHER OR PULPs, THEY

PRODUCE INTERFERON-GAMMA IN

IL10, BUT THESE CALL OUR

ATTENTION CAN PRODUCE LOTS OF

IL10.

OPPOSITE 200 THAT PRODUCE LOTS

OF INTERFERON-GAMMA AND MUCH

LIST IL10 AND AGAIN, YOU

CAN--CAN YOU SEE THE DIFFERENCE

EVEN IN HEALTHY INDIVIDUALS,

THEY HAVE RESPONSE OF TH1 AND

TH2, AND EVEN SOME OF THE

CYTOKINES ARE DIFFERENT

DEPENDING ON THE VECTOR.

AND THIS IS WHAT I--THE LAST

PART, I WANTED TO KNOW IF SOME

OF THE REDOM BIN ANT PROTEINS WE

HAD AND WE STIMULATE THESE

INDIVIDUALS THAT WE'RE PRODUCING

INTERFERON-GAMMA CAN WE FIND A

MOLECULE THAT PRODUCE THE TH1.

AND ACTUALLY, WE FOUND 2.

WE FOUND THAT LGM 11 AND WE

STIMULATE THESE WITH LGM 11 THAT

PRODUCE INTERFERON-GAMMA AND

SOME INDIVIDUALS, A COUPLE

INDIVIDUALS WHERE THE PMC WERE

WITH„i LG7, THEY PRODUCE

INTERFEROG GAMMA AND

[INDISCERNIBLE] WAS STIMULATED

WITH EITHER LGM SPEAN OR LG M

11, THEN, WE WERE EXCITED TO SEE

THESE, THE PROPORTION IS NOT

HIGH, WHICH MEANS THAT THIS

MIGHT NOT BE THE MOST--THE

MOLECULE THAT PRODUCE THE MOST

INTERFERON-GAMMA IN THIS

INDIVIDUAL, BUT WHAT WE FOUND,

ACTUALLY, WE FOUND THE FIRST

DEFINED SALIVA--SALIVAIVEARY

PROTEIN FROM ANY VECTOR ACTUALLY

THAT CAN PRODUCE A TH1 TYPE

SALIVA--SALIVAIVEARY RESPONSE IN

HUMANS.

WE WILL CONTINUE THIS STUDY, WE

ARE IN THE MIDDLE OF THE STUDY,

WE NEED TO TEST THE ASSAY TO SEE

IF THIS IMMUNE RESPONSE, KILL

THE PARASITES AND OTHER MORE

IMMUNOLOGICAL STUDIES BUT THIS

IS WHERE WE'RE GOING RIGHT NOW.

AND JUST TO END, I HOPE TO--THAT

I CONVINCE YOU OF OF THE

IMPORTANCE OF STUDY THANKSGIVING

VECTOR, HOST INTERACTION AND IN

PARTICULAR SALIVA THAT--SALIVA

IS FULL OF THIS POWERFUL

PHARMACOLOGICAL COMPONENTS THAT

BE UTILIZED IN THIS

CARDIOVASCULAR DISEASES FROM THE

SYMPTOMATOLOGY DISEASES AND

VECTOR, IS LIVA VECTOR K'S BE

USED FOR PIG MA TO LOGICAL

VECTORS STUDIES OF BIOMARKERS

WITH THE TOOLS AND THAT SALIVA

CAN PRODUCE THE VERY STRONG

IMMUNE COMPONENT, COMPONENT THAT

CAN MODIFY THE RESPONSE OF THE

HOST OF THE PARASIGHT AND

PROTECTING FOR ANIMALS AGAINST

THE LEASH MANIA AND NOW WE'RE

FINDING THAT THE--THE WAY WE

HUMAN RESPONSE TO SALIVA AND WE

CAN PRODUCE THE TYPE OF

RESPONSES.

THEREFORE, WE ARE HYPOTHESIZING,

OR SUGGESTING THAT SALIVA,

SHOULD BE INCLUDED IN THE

LEISHMANIA VACCINE TOGETHER WITH

THE ANTIGEN AND I THINK WE

SHOULD PUSH FORWARD AND DO MORE

ASSAYS TO TEST THE COMBINATION

OF THE 2 BUT THIS IS SOMETHING

THAT THIS STUDY OF THE ANIMALS

AND HUMANS IS [INDISCERNIBLE].

I WANT TO CLOSE--I NOT GOING TO

TELL EVERYBODY HERE BUT THIS HAS

BEEN A TREMENDOUS JOURNEY

THROUGH ALL THESE YEARS AT THE

NIH AND I WANT TO ACKNOWLEDGE

EVERYBODY IN THE SECTION,

THAT--HAPPY TO MOVE FROM

NONTENURE TO TENURE AND STILL

CONTINUE TO HAVE FUN IN THE LAB

AND TALKING ABOUT SALIVA ALMOST

EVERY DAY.

[INDISCERNIBLE] SCIENTIST IN THE

LAB DOING, I WOULD SAY LIKE

ALMOST CO PI IN MY LAB BECAUSE

HE'S HELPED ME WITH MOST OF THE

PROJECT IN THE LAB.

[INDISCERNIBLE] IS THE RECENT

STAFF SCIENTIST IN THE LAB THAT

IS DOING MOST OF THE STUDIES IN

MALI, AND ALSO

PRODIEDING--PROVIDING GREAT

INSIGHT INTO THE IMEULOGIOLOGY

AND THAT ASPECT.

OUR COLLEAGUE WHO WILL GO TO THE

POSITION IN THE BRAZIL LAB, HAS

BEEN DOING THE STUDY WITH HUMANS

AND DOG ALL THE STUDIES WITH THE

LGM 11 AND THE HAMSTER AND I

WOULD LIKE TO ACKNOWLEDGE THAT I

DID NOT MENTION TODAY,

[INDISCERNIBLE] WITH THE

TRANSMISSION BLOCKING VACCINE,

AND [INDISCERNIBLE] WORKING WITH

DOGS AND SALIVA AND MODELS AND

DR. ANDERSON USED TO BE A MEMBER

OF THE LAB BUT NOW SHE'S A STAFF

SCIENTIST IN MALI, SHE HELPED US

WITH THE PROJECT AND OUR

COLLEAGUE AND POST DOCS THAT ARE

HELPING US A LOT WITH THE

DIFFERENT PRODUCTS AND

[INDISCERNIBLE]--I DIDN'T

MENTION [INDISCERNIBLE] THAT ARE

PART OF THE SAND FLIES WE CANNOT

DO ANY OF THIS TYPE OF RESEARCH.

AND I WANT TO ACKNOWLEDGE

EVERYBODY WITH THE DIFFERENT

LABS, JUST SAY, [INDISCERNIBLE]

AND SUE FOR THE HELP IN THE

DIFFERENT PROJECTS AND ALL THE

OTHER PEOPLE PARTICULARLY THE

GROUP IN MALI THAT HAS BEEN A

TREMENDOUS COLLABORATION.

AND OF COURSE, FUNDING.

MY LAB IS FUNDED BY INTRAMURAL

RESEARCH.

WE GET FUNDS FOR CLINICAL

CENTER, BENCH TO BODY SIDE, AND

WE--BEDSIDE, AND WE GET GOOD

COLLABORATION WITH THE COMPANY,

AND MOST OF THE MONKEY PROJECT

WAS FUNDED BY GATES EXPLORATION

GRANT WITH THIS I'LL FINISH AND

THANK YOU.

[ APPLAUSE ]„i

2K-678.

>> QUESTIONS?

IF YOU CAN'T GET TO THE

MICROPHONE I'LL ASK THEM TO

REPEAT IT BECAUSE WE ARE

TRANSMITTING.

>> A COUPLE WILL OF QUESTIONS,

FIRST OF ALL I WANT TO THANK YOU

FOR THE EXCELLENT PRESENTATION,

I THE QUESTION I HAVE REGUARDING

THE VENUE, YOU SAID WHEN YOU

IMMUNIZE WITH THIS LJ11 MOLECULE

AND THEN YOU CHALLENGE THEM, YOU

DIDN'T SEE MUCH INTERFERON-GAMMA

RESPONSE, IT WAS LOWER.

SO--BUT STILL, THEY WERE

PROTECTED.

SO THE QUESTION IS, IS IT THE

QUALITY OR THE QUANTITY OF THE

INTERFERON-GAMMA THIS IS

IMPORTANT FOR THE PROTECTION AND

TO ANSWER THAT, HAVE YOU DONE

SOME EXPERIMENTS TO SHOW THAT

YOU PUT ANTIINTERFERON-GAMMA AND

TO BLOT THAT AND CAN YOU THEN

SEE BACK AGAIN THE PRODUCTIONS

LOST?

NARKS THATEE 1 QUESTION,.

>> THAT'S A GOOD QUESTION AND

THANK YOU FOR THE OBSERVATION.

THIS IS SOMETHING THAT WE

GOT--WE HAVEN'T DONE ANYTHING

AFTER THAT. WE DID NOT SEE ANY

INTERFERON-GAMMA AT 2 WEEKS BUT

WE SAW IT AT 5 WEEKS.

AT THE BEGINNING BUT STILL

YOU'RE RIGHT.

THAT WAS BIT PUZZLING BECAUSE WE

SEE THE PROTECTION, WE SEE THE

LACK OF OF PATHOLOGY AND THERE

WAS NO INTERFERON-GAMMA AT THAT

TIME POINT.

BUT AS WE SAID, IT CAN BE DUE TO

THE LOW NUMBER OF PARASITES.

BUT BUT--I DON'T HAVE THAT RIGHT

NOW.

BUT WE WILL STUDY THAT.

>> AND I THINK IT WOULD BE

IMPORTANT TO ALSO LOOK AT OTHER

CYTOKINES, YOU KNOW IL17 AND

WHICH ARE--ANTIIPT GREATER

FLAMMATORY RESPONSES AND

CYTOKINES.

SECOND QUESTION, SHOW KHI WAS

VERY INTRIGUING ALSO IS TO--AND

YOU SAID, EVEN THOUGH THE

PARASITE BURDEN S&P REDUCED BUT

THERE ARE STILL PARASITES LEFT

THERE.

THE QUESTION IS IF YOU TREATED

THOSE ANIMALS WITH SOME KIND OF

A DRUG AND YOU GOT RID OF THAT

BECAUSE THAT'S WHAT YOU'RE

REFERRING TO IS HAVING A

PERSISTENT INFECTION IS 1 THAT'S

PROTECTING AND IN A REAL LIFE

SITUATION, AS YOU KNOW VERY

WELL, WE CANNOT HAVE PERSISTENT

PARASITE AS A VACCINE, SO IF YOU

STREETED THEM WITH A DRUG AND

THEN SEE WHETHER YOU CHALLENGE

THEM ARE THEY STILL PROTECTED?

BECAUSE THERE'S THIS CONCEPT

ANIMAL FIST YOU TREAT WITH A

DRUG AND YOU IMMUNE ICE, YOU

KNOW YOU GET A BETTER PROTECTION

OR SOMETHING?

>> THAT'S A VERY GOOD POINT.

WE HAVE NOT ADDRESSED THAT.

WE SHOULD ADDRESS THAT.

ALSO 1 OF THE THINGS WE WANT TO

DO IS REICAL THENCH ANIMAL THAT

IS PROTECT TED BY LGM11.

FIRST WE WANT TO KNOW IF THE

NUMBER OF PARASITE DECREASE FOR

A LOW MEMBER OF RETIREMENT AND

IF YOU DO A RECHALLENGE WITH THE

PARASITE OR THE OTHER PARASITE

THAT IS INDEPENDENT OFMY SALIVA
IF

THE ANIMALS ARE PROTECTED.

WE BELIEVE SO, OR WE HYPOTHESIZE

SO BECAUSE OF WHAT WE SAW 5

WEEKS LATER CHRKS IS CD4 T-CELLS

INTERFERON-GAMMA, ANDLISH MANIA

AND MORE PRODUCE.

THE QUESTION ABOUT THE

PERSISTENT OF THE PARASITE, I

DON'T KNOW BUT IT'S A GOOD

POINT.

THAT'S WHAT I THINK WE SHOULD

TALK ABOUT COMBINING THIS

MUTANTS PARASIGHT WITH SALIVA.

>> I THINK THAT'S A VERY GOOD--

>> THEY CAN GO SHORT TIME, STILL

IMMUNITY,--I MEAN FOR A SHORT

TIME BUT THEN WHEN THE SALIVA

YOU GET THE BARRIER TO THE

PARASITE THAT IS LONG LASTING.

YEAH.

>> I WAS INTERESTED IN SOME OF

YOUR OBSERVATIONS, NUMBER 1 THAT

SOME OF THE PROTEINS COULD BIND

BIOMOLECULES LIKE SEROTONIN AND

THEN 1 OF THE OTHERS THAT YOU

SAY EARLIER THAT 1 OF THEM SEEM

TO REDUCE PAIN THRESHOLDS IN

MICE.

THE 2, QUESTIONS OF A DIFFERENT

SORT, NUMBER 1, I'VE ALWAYS BEEN

CURIOUS WHY USING THE MOSQUITO

AS AN EXAMPLE, YOU CAN GET

BITTEN AND YOU DON'T FEEL

ANYTHING WHICH IS GREAT FOR THE

MOSQUITO, BUT IS IT BECAUSE

THEY'RE RELEASING OR IN THE CASE

OF SAND FLIES, RELEASING

PROTEINS THAT BLOCK YOUR SENSORY

NETWORKS AND ALSO GIVEN THAT THE

1 MIGHT BE ABLE TO REDUCE PAIN

IN MICE, IS THERE ANY POTENTIAL

FOR ANTIPAIN MEDICATIONS OR

MOLECULES.

THAT MIGHT BE OF USE.

>> THE ANSWER TO THE FIRST

QUESTION, THERE IS EVIDENCE OF

AN [INDISCERNIBLE] TYPE

COMPONENT IN THE SALIVA, MANY OF

THESE PROTEINS IF THEY INHIBIT

HISTA MINE OR BRINGING UP OTHER

SALES YOU WILL NOT FEEL THE PAIN

OR YOU WILL NOT FEEL ANYTHING

FOR THE FIRST FEW MINUTES AND

THEN YOU LEAVE AND THEN YOU SEE

THE ACTION.

REGUARDING THE SECOND QUESTION,

YEAH, THERE IS LOTS OF INTEREST

FOR USING SOME OF THESE

MOLECULES FOR ANTIARTHRITIS AND

THIS IS IN COLLABORATION WITH

FERNANDO CUNYA, IN THE LAB OF

THE UNIVERSITY OF

[INDISCERNIBLE] YOU WILL SEE

[INDISCERNIBLE] AND WE HAVE

ACTIVE COLLABORATION, WE PRODUCE

THE PROTEINS AND THEN

GIVING--YOU ON AND I TRANSFER

THESE SEPARATE THINGS TO HIM AND

HE TELLS ME WHICH 1 IS WORKING

AND THEN WE PRODUCE MORE.

THEN THE THING IS SOME OF THESE

PROTEINS HAVE THE DUAL ACTION,

THEY CAN BE'MUNE O GENIC ASK

THEY CAN BE ANTIWHATEVER, BUT

SOME OF THESE PROTEINS ARE VERY

QUIET.

THE SOME ARE NONIMMUNO GENIC

WHICH THESE ARE THE MOLECULES

WE'RE LOOKING FOR AT LEAST FOR

ABET ARTHRITIS, VERY QUIET, KIND

OF STILL INHIBIT AND THIS IS

LGM111, AND WE KNOW THAT HUMAN

FIST WE TEST THE POPULATION IN

BRAZIL, THAT HAVE BEEN EXPOSED

TO BITES AND YOU TEST IT WITH

THE AGAINST LGM111, THEY DON'T

RESPOND AND THAT'S A GOOD

MOLECULE.

>> SO, JESUS, ALONG THE SAME

LINE ALTHOUGH IT'S OBVIOUS WHY

AN INSECT WOULD NOT WANT THE

HOST TO REALIZE THEY'RE BEING

BITTEN, BUT THE LONG-TERM IMMUNO

STIMULATING EFFECTS, IT'S NOT AS

CLEAR UNLESS THE INSECT DOESN'T

WANT THE HOST TO DIE CONVICTLY.

DO HAVE YOU ANY THOUGHT ABOUT

THE EVOLUTION OF THESE PROTEINS

AS POTENT STATE EPT IMMUNO

STIMULANTS AS TO WHY THAT WOULD

BE?

>> WE PUBLISH INDEED 2000, THIS

WAS A POST DOC IN

[INDISCERNIBLE] LAB AND WE HAD

THAT QUESTION.

WE THOUGHT THAT IMMUNITY TO

BITES OF SAND FLIES WAS GOING TO

BE THE TREATMENT OF THE FLIES

BUT THE FLIES WOULD NOT BE

INTERESTED IN FEEDING, WOULD BE

AFRAID OF BITING AND THE POST

WAS GOING TO ATTACK SOMEHOW THE

FLIESS.

ACTUALLY WE FOUND COMPLETELY THE

OPPOSITE, WHAT HAPPENS IS WHEN

THE SAND FLIES PRODUCE, THE TYPE

OF SENSITIVITY RESPONSE, THE

BLOOD FLOW DECREASES

DRAMATICALLY IN THE SITE.

THOSE FLY WHEN IS WE

EXPERIMENTS, WE TOOK IT TO PARTS

OF THE SKIN, WHEN THEY FED IN

OUR BPh SITE, THEY PROP FASTER

40% AND [INDISCERNIBLE] FASTER

45%.

MEASURE BEING TWICE AS FAST IN

PROBING AND FEEDING VERSES A

NONBPh SITE.

THAT'S ADVANTAGEOUS, I DON'T

KNOW HOW A GENETIC BIOLOGIST

WOULD SEE THESE BUT WE TESTED

IT.

WE TESTED THE HYPOTHESIS AND WE

SAW AN ADVANTAGE OF PRODUCING

BPh OF THOSE FLIES.

I DON'T KNOW FOR MOSQUITOES AND

THE OTHERS THERE'S AN ADVANTAGE.

>> SO THE OTHER THOUGHT I HAD IS

THAT THE SAND FLY MIGHT BE A

WONDERFUL VECTOR FOR ACTUALLY

GIVING VACCINES AGAINST OTHER

ORGANISMS, SO IS THERE ANY WORK

GOING ON IN ENGINEERING THE

SALIVARY GLANDS TO PRODUCE

ANTIGENS THAT COULD BE USED

AGAINST LET'S SAY MALARIA.

>> OOH, THAT'S A VERY GOOD

QUESTION.

LEISHMANIASES IS NEGLECTED BUT

THE VECTOR IS VERY NEGLECTED IN

TERMS OF GENETICS.

WE DON'T KNOW HOW TO TRANSFORM

MODEL

MOSQUITOES, THE FIRST RNAi

EXPERIMENTS WERE DONE LAST YEAR,

A COUPLE OF YEARS AGO AND WE

NEED MORE GROUPS INTERESTED IN

THIS ASPECT OF USING SAND FLIES

AS A GENETIC TOOL.

IN TERMS OF USING THE SALIVA OF

THE SAND FLY TO OTHER DISEASES,

YES, WE ARE.

WE ARE INTERESTED IN ANY OTHER

ORGANISMS THAT REQUIRE CD4

T-CELLS FOR PROTECTION.

WE'RE TALKING ABOUT-MARKED FOR

IDENTIFICATION.

>> INDEFINEED VACCINES.

>> YES, I WANT TO VENTURE

[INDISCERNIBLE] CAN WE HELP WITH

THIS TYPE OF MOLECULES THAT HAVE

PROTECTED IMMUNE RESPONSES.

THIS IS SOMETHING THAT IS

CALLING ATTENTION BECAUSE OF THE

POTENCY OF THE MOLECULE WITHOUT

THE ADJUVANT, IT'S

[INDISCERNIBLE] RESPONSE,

OR--WELL IF IT'S CD4 OR DERIVES

THAT PROTECTION TO A PARTICULAR

FORM THAT IS--HA IS PROTECTED,

YES, I WOULD SAY YES.

>> ANY OTHER QUESTIONS?

OKAY.

IF NOT, LET'S THANK JESUS FOR

OPENING OUR EYES TO A WHOLE

BIOLOGY THAT AT LEAST I WAS NOT

FAMILIAR WITH.

[ APPLAUSE ]