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HIV Vaccines: HIV Vaccines: Time for a New VisionTime for a New VisionTime for a New VisionTime for a New Vision
Annie De Groot MDAnnie De Groot MD
EpiVaxEpiVax
GAIA V i F d iGAIA V i F d iGAIA Vaccine FoundationGAIA Vaccine Foundation
Brown University and now . . . Brown University and now . . .
Institute for Immunology and Informatics, Institute for Immunology and Informatics,
University of Rhode IslandUniversity of Rhode Island
i i f i ili i f i ilUniversity of Georgia April 8 2008University of Georgia April 8 2008
AIDS killed AIDS killed 2.5 2.5 million peoplemillion people in in 2007.2007.
During During 2007, 2007, 5 million people became infected 5 million people became infected p pp p
with HIVwith HIVwhich inevitably leads to AIDS which inevitably leads to AIDS
if untreatedif untreatedif untreated.if untreated.
There will There will more than 120 Million more than 120 Million people dying of AIDS in 2010 people dying of AIDS in 2010 There will There will more than 120 Million more than 120 Million people dying of AIDS in 2010. people dying of AIDS in 2010.
Africa, AsiaAfrica, Asia, , disproportionately disproportionately affected . . .affected . . .
The The majoritymajority of people with HIV, some of people with HIV, some 95% 95% of the global total, live of the global total, live in the developing world. in the developing world.
In In 2007, 2007, an estimated an estimated 700,000 700,000 children children In In 2007, 2007, an estimated an estimated 700,000 700,000 children children
O % b bi b t HIVO % b bi b t HIV iti h i d iti h i d O % b bi b t HIVO % b bi b t HIV iti h i d iti h i d
7,7, 7 ,7 ,aged 14 or aged 14 or youngeryounger became infected with HIVbecame infected with HIV.
7,7, 7 ,7 ,aged 14 or aged 14 or youngeryounger became infected with HIVbecame infected with HIV.
Over 90% were babies born to HIVOver 90% were babies born to HIV‐‐positive women, who acquired positive women, who acquired the virus at birth or through their mother's breast milk. the virus at birth or through their mother's breast milk. Over 90% were babies born to HIVOver 90% were babies born to HIV‐‐positive women, who acquired positive women, who acquired the virus at birth or through their mother's breast milk. the virus at birth or through their mother's breast milk.
More than 600,000 of these More than 600,000 of these babies and children babies and children More than 600,000 of these More than 600,000 of these babies and children babies and children live in Africa. live in Africa. live in Africa. live in Africa.
The number of babies dying from AIDS in the US dropped to near The number of babies dying from AIDS in the US dropped to near The number of babies dying from AIDS in the US dropped to near The number of babies dying from AIDS in the US dropped to near zero.zero.zero.zero.
By the end of By the end of 20072007, , the epidemic left behindthe epidemic left behind 20 20 millionmillionAIDS AIDS orphans, who had lost orphans, who had lost one or one or both parents to AIDS both parents to AIDS before before the age of 15.the age of 15.
Treatment is Cost SavingTreatment is Cost SavingTreatment is Cost SavingTreatment is Cost SavingB il d t t ff t f i ti i HIV
350
400ARV purchases Avoided expenditures Final costs
Brazil demonstrates effect of investing in HIV care:
200
250
300
million
100
150
US$ m
‐50
0
50
Cost of antiretroviral drug purchases, avoided expenditures and final costs to the Ministry of Health Brazil, 1997 ‐ 2001*
Source: Ministry of Health Brazil, 2001
* Estimated data1997 1998 1999 2000 2001
The need outstripsThe need outstrips available fundsavailable fundsThe need outstripsThe need outstrips available fundsavailable funds
8,000
10,000International
6,000
8,000National
Private
US$ m
illions
2 000
4,000 Global Fundto Fight AIDS,Tuberculosis andMalaria
2003 2004 2005
U
0
2,000 Malaria
Unmet need
Projected available resources and resource needs in low‐ and middle‐income countries: 2003‐2005
2003 2004 2005
Is asking for treatment for all Is asking for treatment for all ––
. . . “. . . “Too much”?Too much”?Sub‐Saharan Africa: US$3,070M (69.14%)
South and SoutheastAsia: US$670M (15.09%)
East Asia Pacific: East Asia, Pacific: US$80M (1.80%)
Latin America, Caribbean: US$550M (12.39%)
4 Billion for4 Billion for treating HIVtreating HIV//AIDS world wideAIDS world wideandand
Eastern Europe, CentralAsia: US$20M (0.45%)
North Africa, Middle East:
??>500 >500 Billion for Iraq? Billion for Iraq?
Total: Total: US $ 4.4 billionUS $ 4.4 billion,
US$50M (1.13%)
Projected annual expenditure requirements for HIV/AIDS care and support by 2007, by region
Source: Schwartlander B et al (2001) Resource needs for HIV/AIDS, Science
For most of the world, a vaccine is the For most of the world, a vaccine is the For most of the world, a vaccine is the For most of the world, a vaccine is the only hope...only hope...only hope...only hope...
li i li i•• no clinicsno clinics• no doctors• no doctors• no medications• no medications• no condoms• no condoms• what is her chance of • what is her chance of surviving HIV?surviving HIV?
A vaccine could save millions of livesA vaccine could save millions of livesA vaccine could save millions of livesA vaccine could save millions of livesNew adult HIV infections in lowNew adult HIV infections in low‐‐ and middleand middle‐‐income countriesincome countries
5
A vaccine could save millions of livesA vaccine could save millions of livesA vaccine could save millions of livesA vaccine could save millions of lives
Total new infections averted by an AIDS
i b t
Total new infections averted by an AIDS
i b t
4
ns) Vaccine introduction
vaccine between 2015-2030 vaccine between 2015-2030
30% efficacy, 20% coverage 5.5 million30% efficacy, 20% coverage 5.5 million
3
ctio
ns (M
illon Base
Low scenario
17 million50% efficacy, 30% coverage 17 million50% efficacy, 30% coverage
1
2
New
Infe
Medium scenario
70% efficacy, 40% coverage 28 million70% efficacy, 40% coverage 28 million
0
1
2000 2005 2010 2015 2020 2025 2030
High scenario
2000 2005 2010 2015 2020 2025 2030
IAVI impact forecasting; Policy Brief #10, November 2006
Should we be surprised it is taking so Should we be surprised it is taking so l ? V i D ’ l ? V i D ’ i P ii P ilong? Vaccine Dev’t long? Vaccine Dev’t in Perspectivein Perspective
Vaccine Discovery Vaccine YearsVaccine Discovery of Cause
Vaccine Developed
Years Elapsed
Pertussis 1906 1926 20906 9 6 0
Polio 1908 1955 47
Measles 1953 1983 30
Hepatitis A 1973 1995 22
Hepatitis B 1965 1981 16
HIVHIV 19831983 None as yetNone as yet 25 25 and still counting!and still counting!
OutlineOutlineOutlineOutline
Basic aspects of HIV relevant to Basic aspects of HIV relevant to vaccine designvaccine designvaccine designvaccine design
VaccinesVaccines
A new visionA new vision
The HIV VirusThe HIV VirusThe HIV VirusThe HIV Virus
HIV is a HIV is a retrovirusretrovirus: it carries RNA that converts to : it carries RNA that converts to DNA in the infected host cellDNA in the infected host cell
HIV is a HIV is a retrovirusretrovirus: it carries RNA that converts to : it carries RNA that converts to DNA in the infected host cellDNA in the infected host cell
LIFE CYCLE OF HIV 1LIFE CYCLE OF HIV 1LIFE CYCLE OF HIV‐1LIFE CYCLE OF HIV‐1
NucleusNucleusNucleusNucleus
RNARNARNARNA
ReverseReverseReverseReverse
ProteaseProteaseProteaseProtease
DNADNADNADNAReverseReversetranscriptasetranscriptaseReverseReversetranscriptasetranscriptaseHIVHIV
CD4+ T‐CellCD4+ T‐Cell
Entry Entry ‐‐ Binding to CD4 Binding to CD4 and and Chemokine ReceptorChemokine Receptorgg
Two Step Entry Two Step Entry ‐‐Note Variable Loops on gp160 and hidden site of gp41 Note Variable Loops on gp160 and hidden site of gp41 Two Step Entry Two Step Entry Note Variable Loops on gp160 and hidden site of gp41 Note Variable Loops on gp160 and hidden site of gp41
CD4 T cell as HIV FactoryCD4 T cell as HIV FactoryCD4 T‐cell as HIV FactoryCD4 T‐cell as HIV Factory
100 Billion new viral particles per day100 Billion new viral particles per day100 Billion new viral particles per day100 Billion new viral particles per dayp p yp p yp p yp p y
CD T ll d li CD T ll d li i l ii l iCD T ll d li CD T ll d li i l ii l iCD4 T cell decline CD4 T cell decline –– immune paralysisimmune paralysisCD4 T cell decline CD4 T cell decline –– immune paralysisimmune paralysis
Retrovirus process permits evolutionRetrovirus process permits evolutionRetrovirus process permits evolutionRetrovirus process permits evolutionRetrovirus process permits evolutionRetrovirus process permits evolutionRetrovirus process permits evolutionRetrovirus process permits evolution
Reverse TranscriptaseReverse Transcriptase converts this RNA to DNA…but only after converts this RNA to DNA…but only after making numerous mistakesmaking numerous mistakes
Reverse TranscriptaseReverse Transcriptase converts this RNA to DNA…but only after converts this RNA to DNA…but only after making numerous mistakesmaking numerous mistakes
The host cell transcribes and translates the altered HIV DNA, The host cell transcribes and translates the altered HIV DNA, churning out thousands of identical mutant HIV virionschurning out thousands of identical mutant HIV virions
In an HIVIn an HIV infected patient this process occurs simultaneously in infected patient this process occurs simultaneously in
The host cell transcribes and translates the altered HIV DNA, The host cell transcribes and translates the altered HIV DNA, churning out thousands of identical mutant HIV virionschurning out thousands of identical mutant HIV virions
In an HIVIn an HIV infected patient this process occurs simultaneously in infected patient this process occurs simultaneously in In an HIVIn an HIV‐‐infected patient, this process occurs simultaneously in infected patient, this process occurs simultaneously in millions of cells, each generating a different mutant…millions of cells, each generating a different mutant…
There also exists evidence that divergent HIV strains can recombine There also exists evidence that divergent HIV strains can recombine
In an HIVIn an HIV‐‐infected patient, this process occurs simultaneously in infected patient, this process occurs simultaneously in millions of cells, each generating a different mutant…millions of cells, each generating a different mutant…
There also exists evidence that divergent HIV strains can recombine There also exists evidence that divergent HIV strains can recombine ggin a single host, inducing a less frequent but more drastic in a single host, inducing a less frequent but more drastic mutationmutation
ggin a single host, inducing a less frequent but more drastic in a single host, inducing a less frequent but more drastic mutationmutation
HIV EvolutionHIV Evolution
22 ProcessesProcesses BehindBehind HIVHIV EvolutionEvolution
HIV EvolutionHIV Evolution
22 ProcessesProcesses BehindBehind HIVHIV EvolutionEvolution
• genetic drift
l f f• selection for more fit virus variants
TheThe StatsStats
• 109‐1010 virions generated daily
• Mutations = 10‐5 per BP per generation (conservativep p g (estimate)
• HIVGenome ~ 104BP
• > 108 mutant viruses produced every day
Viral Evolution enables escape from T cell recognitionViral Evolution enables escape from T cell recognition
HIV HIV Vi l it b T ll i t t f MHC (HLAVi l it b T ll i t t f MHC (HLA))
Viral Evolution enables escape from T cell recognitionViral Evolution enables escape from T cell recognition
HIV HIV Vi l it b T ll i t t f MHC (HLAVi l it b T ll i t t f MHC (HLA))HIV HIV Viral epitopes are seen by T cells in context of MHC (HLAViral epitopes are seen by T cells in context of MHC (HLA))HIV HIV Viral epitopes are seen by T cells in context of MHC (HLAViral epitopes are seen by T cells in context of MHC (HLA))
Epitope/MHC
Target Cell (CD4 T cell)
Virions
Examples of immune escapeExamples of immune escapep pp p
••These are some These are some published examples published examples p pp pofof epitope epitope escapeescape
hh•• Note that epitopes Note that epitopes can be represented can be represented by strings of lettersby strings of lettersby strings of lettersby strings of letters
Phylogenetic Phylogenetic P6.19.1P6.19.1P6.19.19P6.19.19P6.19.3P6.19.3P6.19.25P6.19.25P6 19 31P6 19 31P6.1.42P6.1.42
Analysis of Analysis of Sequences Sequences
P6.19.31P6.19.31P6.19.28P6.19.28P6.19.29P6.19.29P6.19.30P6.19.30P6.42.3P6.42.3P6.22.16P6.22.16P6 22 4P6 22 4
P6.1.50P6.1.50
44
FromFrom one one PatientPatient
P6.22.4P6.22.4P6.22.5P6.22.5P6.22.3P6.22.3P6.22.6P6.22.6P6.39.2P6.39.2P6.39.4P6.39.4P6.42.17P6.42.17P6.42.17P6.42.17P6.42.23P6.42.23P6.42.1P6.42.1P6.42.19P6.42.19P6.42.7P6.42.7P6.19.4P6.19.4P6.19.5P6.19.5
P6.1.59P6.1.59
9 59 5P6.22.1P6.22.1P6.29.1P6.29.1P6.39.18P6.39.18P6.42.2P6.42.2P6.42.22P6.42.22P6.29.14P6.29.14
P6.1.58P6.1.589 49 4
P6.29.17P6.29.17P6.29.10P6.29.10P6.29.13P6.29.13P6.29.15P6.29.15P6.29.6P6.29.6P6.29.7P6.29.7P6.29.8P6.29.8P6.29.9P6.29.9P6.42.15P6.42.15P6.42.4P6.42.4P6.42.6P6.42.6
Evolution of HIV world wide Evolution of HIV world wide
Adapted from J. MullinsAdapted from J. Mullins
Comparing the variability of HIV, influenza, and HCV Trees drawn on the same scale
Comparing the variability of HIV, influenza, and HCV Trees drawn on the same scale
N = 193, DR CongoGroup M, 1997
Influenza HA geneHA1 domain
D
HN = 20 1997/1998“Sydney-like “Canadian Influenza A
G
N 96 1996 global
J AN = 96 1996 globalH3N2 viruses
F
K
Source: Vidal et al, J.Virol. 1997
CRF01C
,
S S i th ii th iSummary Summary ‐‐ immunopathogenesisimmunopathogenesis
Key points of the lifecycle from the immune (vaccine) Key points of the lifecycle from the immune (vaccine) perspective :perspective :perspective :perspective :
••Near impossible task of preventing HIV entryNear impossible task of preventing HIV entryp p g yp p g y••HIV HIV variability (T and B cell epitopes)variability (T and B cell epitopes)••HIV latency (integration)HIV latency (integration)
f ff f••Destruction of immune defense tissuesDestruction of immune defense tissues••Activation of T cells increases risk of infectionActivation of T cells increases risk of infection
The Simple Approach to HIVThe Simple Approach to HIVp ppp pp
recombinant recombinant proteinprotein(gp120(gp120))VaxgenVaxgena gea ge(and Chiron)(and Chiron)
Some individuals control HIV VLSome individuals control HIV VL
Reduction of “Set Point”Reduction of “Set Point”Walker, AIDS Vaccine 2001Walker, AIDS Vaccine 2001
Potential endPotential end‐‐points of HIVpoints of HIV‐‐vaccine vaccine efficacy trialsefficacy trials
Recall HIV Recall HIV StagesStagesRecall HIV Recall HIV StagesStagesCD8 T cellsCD8 T cells
CD4 T cellsCD4 T cells
CD8 T cellsCD8 T cells
i l i l viral viral loadload
AcuteAcute ChronicChronic AIDSAIDS“flu”“flu” asymptomatic …asymptomatic …. symptomatic. symptomatic
CD4 correlated with Viral load CD4 correlated with Viral load (HIV(HIV‐‐RNA level in plasma)RNA level in plasma)
predicts course of HIV diseasepredicts course of HIV disease
i li l i Si SViral RNAViral RNA Progression to AIDSProgression to AIDS
copies/cccopies/cc within the next 5 yrs.within the next 5 yrs.
<5 000 copies/cc<5 000 copies/cc 8%8%<5,000 copies/cc<5,000 copies/cc 8%8%
5,000 5,000 ‐‐ 13,00013,000 2626%%
13,000 13,000 ‐‐ 36,00036,000 49%49%
>36,000 copies/cc>36,000 copies/cc 62%62%36,000 copies/cc36,000 copies/cc 62%62%
RefRef: Mellors, JW, et al. : Mellors, JW, et al. ScienceScience 272:1167, 1996272:1167, 1996
Vaccines that Vaccines that Suppress HIV?Suppress HIV?
Promise andPromise andProblemsProblems
Larry Corey Larry Corey IAC 2002IAC 2002
Relationship to Viral Load and Relationship to Viral Load and Heterosexual TransmissionHeterosexual TransmissionHeterosexual TransmissionHeterosexual Transmission(Rakai Discordant Couple Trial, n=415)(Rakai Discordant Couple Trial, n=415)
Quinn et al, NEJM 342(13):921‐9, 2000 Mar 30, 34 ( 3) 9 9, 3
eque
ncy
mission
Ann
ual F
reof Trans
mA
RNA Viral Load in HIV+ Source Partner
Mathematical Model of Impact of a Vaccine That Mathematical Model of Impact of a Vaccine That Reduced Viral Load Over TimeReduced Viral Load Over Time
Mathematical Model of Impact of a Vaccine That Mathematical Model of Impact of a Vaccine That Reduced Viral Load Over TimeReduced Viral Load Over Time
(Ira Longini, Emory University)(Ira Longini, Emory University)(Ira Longini, Emory University)(Ira Longini, Emory University)
latio
nlatio
nV in Pop
ulV in Pop
ulen
ce of H
IVen
ce of H
IVPrev
ale
Prev
ale
YearsYears
OutlineOutlineOutlineOutline
Basic aspects of HIV relevant to vaccine designBasic aspects of HIV relevant to vaccine design
VaccinesVaccinesVaccinesVaccines
A new visionA new vision A new visionA new vision
HIV vaccine approachesHIV vaccine approachespppprecombinant protein (gp120)recombinant protein (gp120)
synthetic peptides (V3)synthetic peptides (V3)y p p ( )y p p ( )
naked DNAnaked DNA
livelive--recombinant vectorsrecombinant vectors(viral, bacterial)(viral, bacterial)
wholewhole--inactivated virusinactivated virus
livelive--attenuated virusattenuated virus
Merck Ad5 Vaccine Failure Nov 2007Merck Ad5 Vaccine Failure Nov 2007Merck Ad5 Vaccine Failure Nov 2007Merck Ad5 Vaccine Failure Nov 2007
Titer ALL Low HighALL Low High
Vaccine 49 28 21
Placebo 33 24 9
Vaccine 49 28 21
Placebo 33 24 9
49 HIV infections in the vaccine group and 33 among those who received placebo (Oct 17, 2007).
But in individuals with the highest levels of Ad5 antibody, 21 infections in vaccinees compared to 9 in placebo21 infections in vaccinees compared to 9 in placebo.
Vaccination may not induce T cell recognition of Vaccination may not induce T cell recognition of
HIV HIV Vi l itVi l it t d b h ll t i f it d b h ll t i f i
Vaccination may not induce T cell recognition of Vaccination may not induce T cell recognition of
HIV HIV Vi l itVi l it t d b h ll t i f it d b h ll t i f iHIV HIV Viral epitopesViral epitopes presented by challenge strain of viruspresented by challenge strain of virusHIV HIV Viral epitopesViral epitopes presented by challenge strain of viruspresented by challenge strain of virus
T cell recognitioninduced by vaccine
Target Cell (CD4 T cell)
Challenge Strain
http://chi.ucsf.edu/vaccines
Ongoing HVTN Trials: Phase II
Protocol Number
Status as of December2007
Prime Boost
Class Producer Product Adjuvant Class Producer Product Adjuvant
Ongoing HVTN Trials: Phase II
Class Producer ProductName
Adjuvant Class Producer Product Name
Adjuvant
HVTN 502/Merck 023 (Step) (n=3000)
Closed to accrual
Nonreplicating adenoviral vectors (clade
Merck MRKAd5 trivalent
B Gag-Pol-Nef)
HVTN 204 (n=480) Closed to accrual
DNA plasmids (clade B Gag, Pol, Nef; clade A,B,C Env)
NIH VRC VRC-HIVDNA-016
Non-replicating adenoviral vectors
NIH VRC VRC-ADV-014
, , )(clade B Gag-Pol; clade A,B,C Env)
HVTN 503 (n 801) Cl d t N li ti M k MRKAd5HVTN 503 (n=801) Closed to accrual
Nonreplicating adenoviral vectors (clade B Gag-Pol-Nef)
Merck MRKAd5 trivalent
AIDS Vaccines in Clinical TrialsAIDS Vaccines in Clinical Trials 20072007
DNA vectorsDNA vectors
AIDS Vaccines in Clinical Trials AIDS Vaccines in Clinical Trials -- 20072007
Viral Vectors- Adenovirus
Clade C, Clade C, IAVIIAVI‐‐ADARCADARC
Clade BClade B‐‐minigenesminigenes
Ad-5 (Clade B) Merck
Ad-5 (Clades A,B,C), [DNA] NIH-VRC
Ad-6 (Clade B) Merck
Viral Vectors PoxClade BClade B‐‐minigenesminigenesEpimmuneEpimmune
Clade BClade B‐‐nuclear anchornuclear anchor FIT BiotechFIT Biotech
Clade B, MVA*Clade B, MVA* GeoVaxGeoVax
Viral Vectors- Pox
Canarypox (Clade B/E), gp120* Aventis
MVA (Clade C) IAVI-Therion
MVA* (Clade C) IAVI-ADARC; MulticladeMulticlade‐‐A,B,C, Ad5*A,B,C, Ad5* NIHNIH‐‐
VRCVRC
Clade BClade B‐‐Micro particle, gp140* Micro particle, gp140* ChironChiron
Multiclade, gp120* Multiclade, gp120* U. MassU. Mass
MVA (Clade B),[fowlpox] Therion
MVA (Clade B),[DNA] GeoVax
MVA (Clade A/E), [DNA] WRAIR
MVA (Clade B’/C Changchun Baike, gp, gp
MulticladeMulticlade‐‐ABC, MVA* ABC, MVA* KarolinskaKarolinska
Clade C Clade C Johns Johns HopkinsHopkins
MVA (Clade B /C Changchun Baike
Fowlpox (Clade B)[MVA] Therion
NYVAC (Clade C)[DNA] EuroVac
Vaccinia (Cocktail) St. Jude’s HopkinsHopkins
Clade B’?CClade B’?CChangchun BaikeChangchun Baike
Clade B/C, NYVAC* Clade B/C, NYVAC* EuroVacEuroVac
Viral Vectors- Other
VEE (Clade C) AlphaVax [formerly IAVI]
AAV-2 (Clade C) IAVI-TGEN
Which of these vaccines addresses HIV Which of these vaccines addresses HIV Variability?: HIV is Variability?: HIV is A Global ProblemA Global Problem40 million persons living with HIV/AIDS40 million persons living with HIV/AIDS
Building an HIV vaccine for the worldBuilding an HIV vaccine for the world
OutlineOutlineOutlineOutline
Basic aspects of HIV relevant to vaccine designBasic aspects of HIV relevant to vaccine design
VaccinesVaccines VaccinesVaccines
A new visionA new visionA new visionA new vision
WhatWhat kind of HIV Vaccine?kind of HIV Vaccine?Effective everywhere in the worldEffective everywhere in the world
Against any strain of HIVAgainst any strain of HIV
Broad T cell responseBroad T cell responseBroad T cell responseBroad T cell response
Reduce the chance of transmissionReduce the chance of transmission
Low risk (no live vector)Low risk (no live vector)
Low Cost if not entirely freeLow Cost if not entirely freeLow Cost if not entirely freeLow Cost if not entirely free
Could be made in developing worldCould be made in developing world
ScaleableScaleable
And with collaboration of “developing world” scientistsAnd with collaboration of “developing world” scientists
Th GAIA HIV V iTh GAIA HIV V iTh GAIA HIV V iTh GAIA HIV V iThe GAIA HIV VaccineThe GAIA HIV VaccineThe GAIA HIV VaccineThe GAIA HIV Vaccine
GAIAGAIAGAIAGAIAGlobally relevant globally accessibleGlobally relevant globally accessibleGlobally relevant, globally accessibleGlobally relevant, globally accessible
An EpitopeAn Epitope‐‐Based “World Clade” Based “World Clade” V iV iEpitopes Epitopes ‐‐Minimal Essential Unit of InformationMinimal Essential Unit of InformationEpitopes Epitopes ‐‐Minimal Essential Unit of InformationMinimal Essential Unit of Information
VaccineVaccinep pp p
••Use immunoinformatics to Use immunoinformatics to identify identify “Achilles“Achilles’ heel of HIV’ heel of HIV•• Confirm in context Confirm in context ofof ‘healthy’ HIV‘healthy’ HIV infected patientsinfected patients
p pp p
••Use immunoinformatics to Use immunoinformatics to identify identify “Achilles“Achilles’ heel of HIV’ heel of HIV•• Confirm in context Confirm in context ofof ‘healthy’ HIV‘healthy’ HIV infected patientsinfected patients•• Confirm in context Confirm in context ofof healthy HIVhealthy HIV‐‐infected patientsinfected patients•• Reduce nonReduce non‐‐essential components essential components ‐‐ Limit Limit ToxicityToxicity•• Highly conserved across time and clades of HIVHighly conserved across time and clades of HIV
•• Confirm in context Confirm in context ofof healthy HIVhealthy HIV‐‐infected patientsinfected patients•• Reduce nonReduce non‐‐essential components essential components ‐‐ Limit Limit ToxicityToxicity•• Highly conserved across time and clades of HIVHighly conserved across time and clades of HIV•• Tailored to be presented in HLA of all types of genetic backgroundsTailored to be presented in HLA of all types of genetic backgrounds
And . . . And . . .
•• Tailored to be presented in HLA of all types of genetic backgroundsTailored to be presented in HLA of all types of genetic backgrounds
And . . . And . . .
••Make the vaccineMake the vaccine free of developing world countriesfree of developing world countriesGlobally relevant and globally accessible Globally relevant and globally accessible
••Make the vaccineMake the vaccine free of developing world countriesfree of developing world countriesGlobally relevant and globally accessible Globally relevant and globally accessible Globally relevant and globally accessible Globally relevant and globally accessible Globally relevant and globally accessible Globally relevant and globally accessible
For HIV For HIV ‐‐ variability is a HUGE problemvariability is a HUGE problemy py p
Adapted from J. MullinsAdapted from J. Mullins
Distribution of HIVDistribution of HIV--1 Clades1 Clades
BBFBB
BBF
GBBEEcurrent vaccinescurrent vaccines
AA
E
E
BBE
CCF
GG
H
BBF
BB
EOCC
DDCC
HU
BB
current epidemiccurrent epidemic
source: source: Los Alamos National LaboratoryLos Alamos National Laboratory
“GAIA” HIV Vaccine“GAIA” HIV Vaccine
BBFBB
BBF
GBBEE
AA
E
E
BBE
CCF
GG
H
BBF
BB
EOCC
DDCC
HU
BB
Multiple epitopes that are conserved across cladesMultiple epitopes that are conserved across clades
GAIA Vaccine GAIA Vaccine ‐‐ From From Gene to VaccineGene to Vaccine
In SilicoIn Silico EpiMatrix / ClustiMer / OptiMatrix [class I and class II alleles]EpiMatrix / ClustiMer / OptiMatrix [class I and class II alleles]In SilicoIn Silico EpiMatrix / ClustiMer / OptiMatrix [class I and class II alleles]EpiMatrix / ClustiMer / OptiMatrix [class I and class II alleles]Conservatrix / BlastiMerConservatrix / BlastiMer
In VitroIn Vitro HLA binding assayHLA binding assayIn VitroIn Vitro g yg yELISpot ELISpot -- ELISA ELISA -- Multiplex ELISA Multiplex ELISA -- FACS FACS -- T regulatory T T regulatory T cell profilingcell profiling
In VectorIn Vector DNA vaccinesDNA vaccinesVaccineCADVaccineCADVaccine delivery / formulation optimization / detolerizing Vaccine delivery / formulation optimization / detolerizing delivery agentsdelivery agents
In VivoIn Vivo HLA DR3, DR4 transgenic miceHLA DR3, DR4 transgenic miceIn VivoIn Vivo , g, gHLA class I transgenic miceHLA class I transgenic miceVaccination, Dose, Route, AdjuvantVaccination, Dose, Route, Adjuvant
RPGNTKTVVPCKRPGNKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQAQIQQEEQARPGNTKTVVPCKRPGNKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQAQIQQEEQAQQEKEAMQQQEKEAMQCTRPNNTRKCTRPNNTRKAMYELQKLNSWGTKNLQARYIQYGVYIVTVWGTKNLQRTVRFQTAIEKAMYELQKLNSWGTKNLQARYIQYGVYIVTVWGTKNLQRTVRFQTAIEKYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHARLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTARLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACTRPNNTRKCTRPNNTRKIDRIRERKLTEDRWNKTACHIDRIRERKLTEDRWNKTACH
CTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRKNNCYCKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQALATLITPKQLDCTHLEGKAVFNNCYCKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQALATLITPKQLDCTHLEGKAVFHNFKRKLVDFRELNKPGNTKTVVPCKRPGNKTVPGNKTVVPIGNKTHNFKRKLVDFRELNKPGNTKTVVPCKRPGNKTVPGNKTVVPIGNKT YLKISLNKYYNLRPRQAWCYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAPRQAWCWFKRQAWCWFKWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAPRQAWCWFKRQAWCWFKRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACYLKISLNYLKISLNCTRPNNTRKCTRPNNTRKAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHARLRPGGKKKLARNCRAPPKQIIEQLRLRPGGKKKLARNCRAPPKQIIEQLCTRPNNTRKCTRPNNTRKTKTACNNCYCKRLIDRIRERKLTEDRWNKTACTKTACNNCYCKRLIDRIRERKLTEDRWNKTACELIFQWVQRRPNNYAKIKHTHTDIKQGPKEPSPRTLNAWVGGKKKYRLKQIIEQLIKKKILYQSNPYAELIFQWVQRRPNNYAKIKHTHTDIKQGPKEPSPRTLNAWVGGKKKYRLKQIIEQLIKKKILYQSNPYAAIFQSSMTKPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLAIFQSSMTKPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLCTRPNNTRKCTRPNNTRKYLVSEFPIPHATVLDYLVSEFPIPHATVLD
CTRPNNTRKCTRPNNTRKCTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRKOur approach search for the HIV virus Our approach search for the HIV virus YLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHARLRPRLRPCTRPNNTRKCTRPNNTRKNRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACHNRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACHNNCYCKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQALATLITPKQLDCTHLEGKAVFNNCYCKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQALATLITPKQLDCTHLEGKAVFPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAWTEPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAWTECTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRK
Our approach: search for the HIV virus Our approach: search for the HIV virus “Achilles’ heel” using immunoinformatics“Achilles’ heel” using immunoinformatics
WFHSFNCGGEFTLFCASDAWFHSFNCGGEFTLFCASDACTRPNNTRKCTRPNNTRKPSLYNVATYLVSEFPIPIHAPRQAWCWFKRQAWCWFKPSLYNVATYLVSEFPIPIHAPRQAWCWFKRQAWCWFKRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHARLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTAC
CTRPNNTRKCTRPNNTRKCTRPNNTRKCTRPNNTRK
ELIFQWVELIFQWVCTRPNNTRKCTRPNNTRKIKHTHTDIKQGPKEPSPRTLNAWVGGKKKYRLKQIIEQLIKKKILYQSNPYAIKHTHTDIKQGPKEPSPRTLNAWVGGKKKYRLKQIIEQLIKKKILYQSNPYAAIFQSSMTKPRQAWCWFHSFNCGGEFTLFCASDAKSLWDAIFQSSMTKPRQAWCWFHSFNCGGEFTLFCASDAKSLWDCTRPNNTRKCTRPNNTRKATYLVSEFPIPIHATVLDATYLVSEFPIPIHATVLDYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHARLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTAC
CTRPNNTRKCTRPNNTRKCTRPNNTRKCTRPNNTRK
NNCYCKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQALATLITPKQLDCTHLEGKAVFNNCYCKTVPGNKTVVPIGNKTKVVPITNKTVVPITLYIQYGVYIVLEQALATLITPKQLDCTHLEGKAVFHNFKRKLVDFRELHNFKRKLVDFRELCTRPNNTRKCTRPNNTRKPCKRPGNKTVPGNKTVVPIGNKTPCKRPGNKTVPGNKTVVPIGNKT YLKISLNKYYNLRPRQAWCYLKISLNKYYNLRPRQAWCWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAPRQAWCWFKRQAWCWFKWFHSFNCGGEFTLFCASDAKSLWDQSLKPSLYNVATYLVSEFPIPIHAPRQAWCWFKRQAWCWFKRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTACRLRPGGKKKLARNCRAPPKQIIEQLIKKAIFQSSMTKTACNNCYCKRLIDRIRERKLTEDRWNKTAC
CTRPNNTRKCTRPNNTRK
Conservatrix: Find conserved epitopes in variable Conservatrix: Find conserved epitopes in variable th (thi k HIV HCV t )th (thi k HIV HCV t )pathogens (think HIV, HCV etc.)pathogens (think HIV, HCV etc.)
CTRPNNTRKCTRPNNTRK
ConservedConserved
CTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRKCTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRKCTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRK
HIV protein sequencesHIV protein sequences
ConservedConservedepitopeepitope
CTRPNNTRKCTRPNNTRK
CTRPNNTRKCTRPNNTRK
T help essential; T help essential; Conserved T help an obstacleConserved T help an obstacle
“Th l f HIV i f l d t t t “Th l f HIV i f l d t t t “The goal of an HIV vaccine for one clade to protect “The goal of an HIV vaccine for one clade to protect against other clades may be more limited by the against other clades may be more limited by the ability to provide CD4 T cell help than the ability to ability to provide CD4 T cell help than the ability to li it CD8 ff t f ti ”li it CD8 ff t f ti ”elicit CD8 effector functions.”elicit CD8 effector functions.”
Smith JM, Amara RR, Wyatt LS, Ellenberger DL, Li B, Herndon JG, Patel M, Sharma S, Smith JM, Amara RR, Wyatt LS, Ellenberger DL, Li B, Herndon JG, Patel M, Sharma S, Chennareddi L, Butera S, McNicholl J, McClure HM, Moss B, Robinson HL. Studies in Chennareddi L, Butera S, McNicholl J, McClure HM, Moss B, Robinson HL. Studies in macaques on crossmacaques on cross‐‐clade T cell responses elicited by a DNA/MVA AIDS vaccine, better clade T cell responses elicited by a DNA/MVA AIDS vaccine, better conservation of CD8 than CD4 T cell responses. AIDS Res Hum Retroviruses. 2005 conservation of CD8 than CD4 T cell responses. AIDS Res Hum Retroviruses. 2005 Feb;21(2):140Feb;21(2):140‐‐4. 4.
i ii iImmunogenic Consensus EpitopesImmunogenic Consensus Epitopes
ConservedConservedepitope epitope
CTRPNNTRKCTRPNNTRK
Conserved epitopesConserved epitopes
p pp p
EpiEpi‐‐AssemblerAssembler
Immunogenic consensusImmunogenic consensus
A A Time
Aggregate Aggregate of of ideal ideal
Aggregatrix:Aggregatrix:
ideal ideal epitopesepitopes
Aggregatrix:Aggregatrix:Using our tools, we Using our tools, we have found HIV have found HIV epitopes that are epitopes that are p pp phighly conserved highly conserved over time over time andandacross HIV subtypesacross HIV subtypes
Current GAIA Epitope SummaryCurrent GAIA Epitope SummaryCurrent GAIA Epitope SummaryCurrent GAIA Epitope Summary
> 400 epitopes mapped> 400 epitopes mapped> 400 epitopes mapped> 400 epitopes mapped> 300 tested (ELIspot)> 300 tested (ELIspot)> 200> 200 confirmed (>67%)confirmed (>67%)> 200 > 200 confirmed (>67%)confirmed (>67%)HLA A2, A3, A24, B7, B44 and Class II (clustered)HLA A2, A3, A24, B7, B44 and Class II (clustered)
Both Supertype and Promiscuous EpitopesBoth Supertype and Promiscuous Epitopes
Improving Vaccine Design by aligning epitopesImproving Vaccine Design by aligning epitopes: Vaccine: Vaccine‐‐CADCAD
1 2 3Design the arrangement of the epitopes to minimize the immunogenicity of Design the arrangement of the epitopes to minimize the immunogenicity of junctional peptides and focus the immune response to the desired epitopesjunctional peptides and focus the immune response to the desired epitopesDesign the arrangement of the epitopes to minimize the immunogenicity of Design the arrangement of the epitopes to minimize the immunogenicity of junctional peptides and focus the immune response to the desired epitopesjunctional peptides and focus the immune response to the desired epitopes
1 2 3
De Groot AS, Marcon L, Bishop EA, Rivera D, Kutzler M, Weiner DB, Martin W.HIV vaccine development by computer assisted design: the GAIA vaccine. Vaccine. 2005
Immunome VaccineImmunome VaccineConstruct Design / AssemblyConstruct Design / Assemblyg / yg / y
Intended Protein Product: Many epitopes strung together in a “StringIntended Protein Product: Many epitopes strung together in a “String‐‐ofof‐‐Beads”Beads”
Reverse Translation: Determines the DNA sequence necessary to code for the intended Reverse Translation: Determines the DNA sequence necessary to code for the intended protein This DNA is assembled for insertion into an expression vectorprotein This DNA is assembled for insertion into an expression vectorprotein. This DNA is assembled for insertion into an expression vector.protein. This DNA is assembled for insertion into an expression vector.
DNA insertDNA insert
DNA DNA VectorVector
Protein Protein product product (folded)(folded)
EpitopeEpitope‐‐based vaccines Protect based vaccines Protect HLA DR Mice HLA DR Mice from 5X LDfrom 5X LD LVS ChallengeLVS Challengefrom 5X LDfrom 5X LD5050 LVS ChallengeLVS Challenge
FT_II_v1-immunized Mice
PlaceboRecipient MiceRecipient Mice
GAIA Vaccine CollaborationGAIA Vaccine CollaborationLaboratoire de la Biologie Moleculaire Applique Laboratoire de la Biologie Moleculaire Applique
Dr. Ousmane Koita (FAST) U. BamakoDr. Ousmane Koita (FAST) U. Bamako
Hope Center Clinic, Hope Center Clinic, Sikoro . . . Sikoro . . . 20052005
Hope Center Clinic (Centre D’Espoir)Hope Center Clinic (Centre D’Espoir)Hope Center Clinic (Centre D Espoir)Hope Center Clinic (Centre D Espoir)Front line HIV care and Prevention Front line HIV care and Prevention ––GAIA Vaccine FoundationGAIA Vaccine Foundation
. . . . . . 20082008
Wh ill h Wh ill h When will we have When will we have anan HIV Vaccine?HIV Vaccine?
Phases of HIV vaccine trialsPhases of HIV vaccine trialsPhases of HIV vaccine trialsPhases of HIV vaccine trials
Phase Sample I/E criteria Endpoints DurationPhase Sample I/E criteria Endpoints Duration
I 20-50 Healthy, HIV-uninfected at lower risk for HIV-
Safety,preliminary
18-24 mat lower risk for HIV-infection; dose, regimen
preliminary Immunogencity
II 200-500 (Healthy), HIV- Safety, 18-24 muninfected at lower to higher risk, dose; regimen
Immunogencity
III 5000 HIV i f t d t i k E d d 3 5III 5000-10.000
HIV-uninfected, at risk (CSW, discordant couples, general population)
Expanded safety EfficacyCorrelates of
3-5 years
p p ) Correlates of protection
10 years
Potential Availability Of Efficacy Data Potential Availability Of Efficacy Data F C t & Pl d T i l *F C t & Pl d T i l *From Current & Planned Trials*From Current & Planned Trials*
2004 2005 2006 20112007 2008 2009 201020033 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4
♦
2004 2005 2006 2011
RV 144
2007 2008 2009 20102003
♦
♦
♦
Merck 023/HVTN 502 (STEP)
HVTN 503
PAVE 100 ♦
Enrollment Follow-up
EP 44 503
100
PAVE 100
STE
RV
14
HVT
N 5
PAVE
1
Anticipated Data Availability
Courtesy, J Flores*Assuming no early termination
AIDS Vaccines in Preclinical Pipeline 2007AIDS Vaccines in Preclinical Pipeline 2007
NIAID/CHAVINIAID/CHAVI
AIDS Vaccines in Preclinical Pipeline - 2007AIDS Vaccines in Preclinical Pipeline - 2007
In trials 2007In trials 2007 20092009 NIAID/CHAVINIAID/CHAVIChimeric Adeno VectorsChimeric Adeno Vectors
BCGBCG
VSVVSV
In trials 2007In trials 2007--20092009
Ad 35 prototypeAd 35 prototype NIHNIH--VRCVRC
Ad 35Ad 35 IAVIIAVI--CrucellCrucellVSVVSV
Adeno: Chimeric and AdAdeno: Chimeric and Ad‐‐1111
Pox: NYVAC, MVAPox: NYVAC, MVA
Low seroLow sero‐‐prevalent AAV prevalent AAV
Chimeric AdenoChimeric Adeno HarvardHarvard--CrucellCrucell
VSVVSV WyethWyeth
MeaslesMeasles GSKGSK pp
Reovirus Reovirus
Newcastle Disease Newcastle Disease
HIV/VEE Chimeras HIV/VEE Chimeras
MVAMVA SAAVISAAVI; WRAIR; WRAIR
HIV/VSV ChimerasHIV/VSV Chimeras
BCGBCG
IAVI Vector ProgramIAVI Vector Program
SendaiSendai
CMVCMV
Simian Adeno (GSK)Simian Adeno (GSK)
GAIA Vaccine Status: GAIA Vaccine Status: Now “Pre Phase I”Now “Pre Phase I”
286 highly conserved HIV CTL/ Th epitopes mapped286 highly conserved HIV CTL/ Th epitopes mapped
186 epitopes in the last three years186 epitopes in the last three years86 ep topes t e ast t ee yea s86 ep topes t e ast t ee yea s
149 confirmed149 confirmed
10 constructs synthesized10 constructs synthesizedyy
6 tested (4 A2 AAY+/6 tested (4 A2 AAY+/‐‐; 2 Class II = original/reorderd); 2 Class II = original/reorderd)
3 work! Positive responses in HLA transgenic mice3 work! Positive responses in HLA transgenic mice3 p g3 p g
More constructs in progressMore constructs in progress
Phase I trial preparation in Mali, W. AfricaPhase I trial preparation in Mali, W. Africa
AIDS DeathsAIDS DeathsAIDS DeathsAIDS Deaths
Http://www.worldmapper.org
Health SpendingHealth SpendingHealth SpendingHealth Spending
A l b t l tiA l b t l tiMore resources are being invested …more neededMore resources are being invested …more needed
Annual average by country relative to national wealth (2003-2005)Annual average by country relative to national wealth (2003-2005)
I t t i AIDS i R&D
Philanthropic
Total over 2005 = US$759 mnTotal over 2005 = US$759 mn % of GDP (x10-3)
Country
4.0 – 5.0 United States
Investment in AIDS vaccine R&D
US Public
pSector
US$12 mn
Commercial Sector
US$75
2.0 – 3.0
1.0 – 2.0
Ireland
CanadaSouth AfricaNetherlands
3.0 – 4.0
Sector US$574 mn
US$75 mn
Non-US Public Sector
US$98
0.5 – 1.0
Netherlands
NorwayUnited Kingdom
DenmarkSweden
US$98 mn
< 0.5
AustraliaBrazilChinaFinlandFranceGermany
IndiaItalyJapanRussiaThailand
Based on a 2006 study by the HIV Vaccines and Microbicides Resource Tracking Working Group; full report available at: www.hivresourcetracking.org. The study reviewed national, not sub-national or provincial, public sector data. Cuba is not captured as no GDP data is available. Estimates of 2005 investment include NIH CHAVI funds but not Gates Grand Challenges/ Gates Foundation
Germany
War BudgetWar Budget
Spending on War 2008Spending on War 2008
War BudgetWar Budget
Spending on War 2008
= $1.4 TRILLION (US = $711 B)
Global spending on AIDS Vaccines
Spending on War 2008
= $1.4 TRILLION (US = $711 B)
Global spending on AIDS Vaccines
= $759 M
= 0.1 % of amount spent on war.
= $759 M
= 0.1 % of amount spent on war.
A safe, effective and globally accessible AIDS vaccine is possible. A safe, effective and globally accessible AIDS vaccine is possible. One day it could save the lives of tens of millions of people. One day it could save the lives of tens of millions of people.
But AIDS has not benefited from the same level of public or political support that But AIDS has not benefited from the same level of public or political support that propelled the war on polio.propelled the war on polio.
The March of Dimes crusade started in 1930. By 1955 The March of Dimes crusade started in 1930. By 1955 ––25 years later 25 years later ‐‐we had a we had a vaccine. vaccine.
25 years later 25 years later ‐‐we cannot say the same about AIDS. we cannot say the same about AIDS.
Jon Cohen, science writer who has followed the field for more than 20 years says Jon Cohen, science writer who has followed the field for more than 20 years says Jon Cohen, science writer who has followed the field for more than 20 years says Jon Cohen, science writer who has followed the field for more than 20 years says that AIDS vaccine researchers are always strapped for funds, and their funds are that AIDS vaccine researchers are always strapped for funds, and their funds are mainly allocated by their publication record. Instead of thinking mainly allocated by their publication record. Instead of thinking –– how do I make a how do I make a vaccine faster vaccine faster –– they are thinking they are thinking ‐‐ 'What can I publish next?'" 'What can I publish next?'" y gy g pp
In fact, research spending on AIDS vaccines today totals only approximately US In fact, research spending on AIDS vaccines today totals only approximately US $700 $700 million dollars a year, about the cost ofmillion dollars a year, about the cost of five five Hollywood movies. Hollywood movies.
Where Where is our March of Dimes for an AIDS Vaccine?is our March of Dimes for an AIDS Vaccine?
Is Is this asking for “Too much”?this asking for “Too much”?. . . Is . . . Is this asking for Too much ?this asking for Too much ?
One vaccine, start to finish: One vaccine, start to finish: 2o Million 2o Million
Ours: already part way thereOurs: already part way there
Yet >500 Billion for Iraq? http://www.nationalpriorities.org/costofwar_home Yet >500 Billion for Iraq? http://www.nationalpriorities.org/costofwar_home
Hope is a vaccineHope is a vaccineHope is a vaccineHope is a vaccine
http:www.gaiavaccine.org
Alliance Globale pour la Lutte contre le SIDAAlliance Globale pour la Lutte contre le SIDA
•• Espoir/Hope Espoir/Hope -- SIDA n’est pas la Mort/AIDS is not DeathSIDA n’est pas la Mort/AIDS is not Death•• IdentitIdentitéé DDéépistage pistage -- Get Tested Get Tested •• Transmission Transmission PrPréévention vention -- Stop TransmissionStop Transmission•• Famille/FidelitFamille/Fidelité/Femmeé/Femme Family/Few Partners/MTCTPFamily/Few Partners/MTCTP
Hope is a Vaccine / Tenez a l’Espoir http://www.GAIAVaccine.org
•• Famille/FidelitFamille/Fidelité/Femmeé/Femme Family/Few Partners/MTCTPFamily/Few Partners/MTCTP•• CommunuatCommunuatéé Together we can stop HIVTogether we can stop HIV