AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period
Yunda Huang, Kelly E Seaton, Martin Casapia, Laura Polakowski, Stephen C De Rosa, Kristen Cohen, Chenchen Yu, Marnie Elizaga, Carmen Paez, Maurine D Miner, Colleen F Kelley, Janine Maenza, Michael Keefer, Javier R Lama, Magdalena Sobieszczyk, Susan Buchbinder, Lindsey R Baden, Carter Lee, Vineeta Gulati, Faruk Sinangil, David Montefiori, M Juliana McElrath, Georgia D Tomaras, Harriet L Robinson, Paul Goepfert, NIAID-funded HIV Vaccine Trials Network (HVTN) 114 Study Team, Yunda Huang, Kelly E Seaton, Martin Casapia, Laura Polakowski, Stephen C De Rosa, Kristen Cohen, Chenchen Yu, Marnie Elizaga, Carmen Paez, Maurine D Miner, Colleen F Kelley, Janine Maenza, Michael Keefer, Javier R Lama, Magdalena Sobieszczyk, Susan Buchbinder, Lindsey R Baden, Carter Lee, Vineeta Gulati, Faruk Sinangil, David Montefiori, M Juliana McElrath, Georgia D Tomaras, Harriet L Robinson, Paul Goepfert, NIAID-funded HIV Vaccine Trials Network (HVTN) 114 Study Team
Abstract
Background: Eliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses.
Methods: We enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5).
Results: All regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag.
Conclusions: Late boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine.
Keywords: AIDSVAX; DNA Vaccine; HIV vaccine; Late boost; MVA vaccine; V1V2 antibody.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors of this manuscript have read the journal's policy and have the following competing interests: YH, CY, MDM, CP, SCD, KC, MJM, PG, JM, MK, MS, LRB, DM are recipients of funding from The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health, and this publication is a result of activities funded by the NIAID. HLR was a co-founder of GeoVax, Inc. and is an inventor on patents that GeoVax licensed from Emory University and the NIAID for commercial development of the MVA/HIV62B and JS7 DNA vaccines. CFK receives research grants to her institution from NIH, CDC, Gilead Sciences, ViiV, Moderna, and Novavax. GDT received research grants to her institution from NIAID, BMGF, GSK and Macrogenics, has patent applications for HIV vaccine design and incidence testing, and has consulted for Axon Advisors. KES has a patent application for HIV incidence testing. SB receives research grants to her institution from NIH, Gilead Sciences, Merck, and Viiv. The rest of the authors have no conflicts.
Published by Elsevier Ltd.
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Source: PubMed