Martin Freeman, Untitled Diagnosed with AIDS in 1990, Martin lives in San Francisco where he continues to create new pieces. Hanneke Schuitemaker VP, Head Viral Vaccine Discovery and Translational Medicine, Janssen Vaccines and Prevention B.V. Professor in Virology at the Academic Medical Center, University of Amsterdam IAS | Paris, 24 July 2017 Evaluation of lead HIV-1 vaccine regimen in APPROACH: Phase 1/2a study testing heterologous prime boost regimens using mosaic Ad26 and MVA vectors combined with Env protein
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Martin Freeman, UntitledDiagnosed with AIDS in 1990, Martin lives in
San Francisco where he continues to create new pieces. Hanneke SchuitemakerVP, Head Viral Vaccine Discovery and Translational Medicine, Janssen Vaccines and Prevention B.V.Professor in Virology at the Academic Medical Center, University of AmsterdamIAS | Paris, 24 July 2017
Evaluation of lead HIV-1 vaccine regimen in APPROACH: Phase 1/2a study testing heterologous prime boost regimens using mosaic Ad26 and MVA vectors combined with Env protein
Heterologous prime-boost vaccine regimens: tested in early studies in parallel in humans (phase 1/2a study HIV-V-A004/ IPCAVD009/APPROACH) and in NHP (study #13-19)
Studies that inform decision to proceed with a Phase 2b/Proof of Concept study
Safety/Immuno
Post3rd vacc
Safety/Immuno
Post4th vacc
Safety/Immuno
Post2nd and3rdvacc
NHPStudy13-19
Efficacy/correlates
Phase2aAPPROACH
Phase2aTRAVERSE
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The Ad26/Ad26+gp140 HIV Vaccine Regimen Provided Significant Protection Against SHIVSF162P3Challenges in NHP (study 13-19*)
0 2 4 60
20
40
60
80
100
week post first challenge
Perc
ent u
ninf
ecte
d Ad prime /Ad boostAd prime /gp140 boostAd prime /Ad+gp140 boostAd prime /MVA boostAd prime /MVA+gp140 boost
Sham
*Statistically significant vs Sham in a Cox proportional hazard model and Log-rank test; †Statistically significant vs Sham in a 2-sided Fisher’s exact test
Studies that inform decision to proceed with a Phase 2b/Proof of Concept study
Safety/Immuno
Post3rd vacc
Safety/Immuno
Post4th vacc
Safety/Immuno
Post2nd and3rdvacc
NHPStudy13-19
Efficacy/correlates
Phase2aAPPROACH
Phase2aTRAVERSE
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Phase 1/2a: APPROACH
FIH of Ad26.Mos.HIVand heterologous regimens
Countries: USA, Rwanda, Uganda, South Africa, ThailandTarget N: 400Sponsor: Janssen Vaccines*Partners: BIDMC*, IAVI*, MHRP*, HVTN/NIAID*, Ragon**co-funders
APPROACH: The path or route to the start of a technical climb. Although this is generally a walk or,
at most, a scramble it is occasionally as challenging as the climb itself
+Alum
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Phase 1/2a with tetravalent Ad26 and Mosaic gp140: TRAVERSE and ASCENT
§ HPX2004/ HVTN117 / TRAVERSEAd26.Mos4.HIV (4-valent) vs Ad26.Mos.HIV (3-valent)
Countries: USA, RwandaTarget N: 198Sponsor: Janssen Vaccines*Partners: BIDMC*, BMGF*, HVTN/NIAID*, MHRP*, Ragon**co-funders TRAVERSE: progress forward by moving horizontally
§ HPX2003/ HVTN 118 / ASCENTAd26.Mos4.HIV and Mosaic gp140 + Clade C gp140 vs Ad26.Mos4.HIV and Clade C gp140 alone
Countries: USA, Rwanda, KenyaTarget N: 150Sponsor: Janssen VaccinesPartners: BIDMC*, HVTN/NIAID*, MHRP*, Ragon**co-funders ASCENT: a walk to the summit of a mountain
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§ Selection of criteria based on:– Immune correlates of protection identified in NHP studies
§ Emphasis on:– Vaccine take as demonstrated by humoral and cellular immune responses– Magnitude of humoral and cellular immune responses – Functionality of elicited antibodies
From Phase 1/2a to Proof of Concept studypre-specified Go/no-Go criteria
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In addition functional antibodies, as assessed by ADCP, were found to correlate with protection, as has been observed in previous studies and are considered supportive
Binding antibodies to HIV Env together with HIV Env specific T cells correlated with protection in NHP SHIVSF162P3 challenge study
UninfectedInfected
Shaded colors and diagonal lines indicate the probability of infection modeled on ELISpot and ELISAresponses
InfectionstatusatChallenge#3
wk28EnvELISA
(log10)
wk26ELISpot (log10)
JennyHendriks,IASHVTNSatellite,25July- 7am
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• InordertomovetoaPoC efficacystudy,theELISAand ELISPOT criteriahavetobemet• TheADCP criteria,Magnitudes and Envboostareconsideredsupportive