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OA-033
THE RESULTS OF THE EV06 DNA-PROTEIN COMBINATION TRIAL AND PLANS FOR GREAT, AN EDCTP2-FUNDED CONSERVED-MOSAIC EPITOPE HIV VACCINE TRIAL
  1. Pontiano Kaleebu1,
  2. Jonathan Levin1,
  3. Annet Nanvubya2,
  4. Freddie Kibengo1,
  5. Walter Jaoko3,
  6. Pietro Pala1,
  7. Matthieu Perreau4,
  8. Annemarie Namuniina2,
  9. Paul Kitandwe2,
  10. Gonzalo Tapia4,
  11. Jennifer Serwanga1,
  12. Nicole Yates5,
  13. Pat Fast6,
  14. Bryan Mayer7,
  15. David Montefiori5,
  16. Georgia Tomaras5,
  17. Merlin Robb8,
  18. Carter Lee9,
  19. Ralf Wagner10,
  20. Edward Sanders11,
  21. William Kilembe12,
  22. Noah Kiwanuka2,
  23. Jill Gilmour6,13,
  24. Hester Kuipers6,
  25. Dani Vooij6,
  26. Kundai Chinyenze6,
  27. Frances Priddy6,
  28. Song Ding14,
  29. Tom Hanke15,
  30. Giuseppe Pantaleo4,16,
  31. EV06 study team GREAT study team1
  1. 1MRC-UVRI AIDS, Uganda
  2. 2UVRI-IAVI HIV Vaccine Program, Uganda
  3. 3University of Nairobi, Kenya
  4. 4CHUV, Switzerland
  5. 5Duke University, United States of America
  6. 6IAVI, United States
  7. 7Fred Hutchinson Cancer Research Center, United States of America
  8. 8MHRP, United States
  9. 9GSID, United States of America
  10. 10Universität Regensburg, Germany
  11. 11KEMRI, Kenya
  12. 12ZEHRP, Zambia
  13. 13Imperial College London, United Kingdom
  14. 14EuroVacc Foundation, Switzerland
  15. 15University of Oxford, United Kingdom
  16. 16SVRI, Switzerland

Abstract

Background These two trials under Europe-Africa collaborations aim at addressing two factors relevant for Africa i.e helminth infections and HIV-1 diversity. EV06 used a novel combination of DNA expressing clade C Env, Gag and Pol-nef co-administered with AIDSVAX®B/E Env protein to study the effect of S. mansoni on vaccine responses. GREAT is a recently awarded trial using a 2nd generation improved conserved tHIVConsvX T-cell vaccine candidate combined with bivalent mosaic design to increase breadth and protective epitopes.

Methods EV06 enrolled 72 males and females aged 18–45, half infected with S. mansoni (SM+). In each arm 30 received vaccine and 6 placebo at week 0, 4 and 24. Responses were evaluated at week 0, 6, 26 and 36. Humoral responses were measured as binding IgG against a panel of HIV-1 envelope glycoproteins and as neutralizing antibodies (Nabs), using TZM/ bl cells and tier 1 pseudoviruses. Cellular responses were measured as HIV-specific CD4+ and CD8+ T-cell by IFN-γ ELIS-pot and multi-cytokine intracellular staining flow cytometry. GREAT will be a phase IIa trial and preparation for efficacy trials in Kenya, Uganda and Zambia testing ChAdOx1.tHIVconsv5 and ChAdOx1.tHIVconsv6 followed by MVA.tHIVconsv3 and MVA.tHIVconsv4 on week 2 (Arm 1) or week 8 (Arm 2).

Progress Differences in binding IgG response rates were observed in vaccinated participants against the vaccine matched clade C V1V2 (gp70–96ZM651.02 V1V2) at week 6: 56% among SM+ versus 86% among SM – (p=0.039). At week 36, response magnitudes were statistically lower in the SM+ against gp120 and gp140 proteins (p=0.04 for both). SM+ also had lower Nabs and ELISpot responses at various time points. Still blinded data on the first 20 volunteers show 80% responders for CD4 T cell at w26 and 70% CD8 responders at w36. These trials will provide more data on challenges facing HIV vaccine development in Africa.

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