Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1–2 randomized double-blind placebo-controlled trial

Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding antibody and T-cell responses were similar or greater at month 12.5 vs. month 6.5, but waned by month 18, we investigated vaccine-elicited immune responses after a month 30 boost in this study, HVTN 100 Part B. From 13 September 2017 to 7 August 2018, a subgroup of vaccinees was randomized to receive intramuscular injections of ALVAC+gp120/MF59 (n = 32) or gp120/MF59 alone (n = 31) and a subgroup of placebo recipients was administered placebo (n = 7) at month 30. Primary outcomes were safety, IgG binding antibodies (bAbs) to vaccine-specific and V1V2 Env proteins and vaccine-specific CD4+ T cells at month 30.5. Secondary outcomes included neutralizing and antibody dependent cellular cytotoxicity functions and durability at months 30 and 36. Both vaccine groups had an acceptable safety profile. There were no statistically significant differences in the occurrence or level of IgG bAbs between the vaccine boost groups for any vaccine-specific or V1V2 antigens. IgG responses were higher to vaccine-matched gp120 than to V1V2. The booster vaccination restored the magnitude-breadth IgG bAb response to V1V2 antigens at month 30.5. However, it rapidly waned by month 36. CD4+ T-cell response rates to the 3 vaccine-matched Env antigens for the combined vaccine groups ranged from 37% at month 30, boosted to as high as 91% at month 30.5, and waned by month 36 to as low as 44%, with no significant differences between the vaccine boost groups. Because these responses waned after 6 months, additional strategies may be needed to maintain the durability of prime-boost vaccine regimens and to generate these or other immune responses that confer protection. Trial registration: South African National Clinical Trials Register (SANCTR number: DOH-27-0215-4796) and ClinicalTrials.gov (NCT02404311).

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PLOS Global Public Health
Published
2024-09-20
DOI
https://doi.org/10.1371/journal.pgph.0003319
Primary Topic
HIV Research and Treatment
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article
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article

Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1–2 randomized double-blind placebo-controlled trial

Sanjay Gurunathan, Kelly E. Seaton, David C. Montefiori, Mookho Malahleha et al.
PLOS Global Public Health
HIV Research and Treatment
article

Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1–2 randomized double-blind placebo-controlled trial

Sanjay Gurunathan, Kelly E. Seaton, David C. Montefiori, Mookho Malahleha, Olivier Van Der Meeren, Nicole Grunenberg, Zoe Moodie, Maurine D. Miner, Brodie Daniels, Vimla Naicker, Craig Innes, Nonhlanhla N. Mkhize, Marguerite Koutsoukos, Alison C. Roxby, Linda‐Gail Bekker, Tandile Modise, Stephen De Rosa, Guido Ferrari, Valerie Bekker, Fatima Laher, Nicole L. Yates, Chenchen Yu, Jack Heptinstall, Kathryn Therese Mngadi, Kevin O. Saunders, Briana D. Furch, M. Juliana McElrath, Lynn Morris, Carlos A. DiazGranados, Mary Allen, Georgia D Tomaras, Sanjay Phogat
article en

Abstract

Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding antibody and T-cell responses were similar or greater at month 12.5 vs. month 6.5, but waned by month 18, we investigated vaccine-elicited immune responses after a month 30 boost in this study, HVTN 100 Part B. From 13 September 2017 to 7 August 2018, a subgroup of vaccinees was randomized to receive intramuscular injections of ALVAC+gp120/MF59 (n = 32) or gp120/MF59 alone (n = 31) and a subgroup of placebo recipients was administered placebo (n = 7) at month 30. Primary outcomes were safety, IgG binding antibodies (bAbs) to vaccine-specific and V1V2 Env proteins and vaccine-specific CD4+ T cells at month 30.5. Secondary outcomes included neutralizing and antibody dependent cellular cytotoxicity functions and durability at months 30 and 36. Both vaccine groups had an acceptable safety profile. There were no statistically significant differences in the occurrence or level of IgG bAbs between the vaccine boost groups for any vaccine-specific or V1V2 antigens. IgG responses were higher to vaccine-matched gp120 than to V1V2. The booster vaccination restored the magnitude-breadth IgG bAb response to V1V2 antigens at month 30.5. However, it rapidly waned by month 36. CD4+ T-cell response rates to the 3 vaccine-matched Env antigens for the combined vaccine groups ranged from 37% at month 30, boosted to as high as 91% at month 30.5, and waned by month 36 to as low as 44%, with no significant differences between the vaccine boost groups. Because these responses waned after 6 months, additional strategies may be needed to maintain the durability of prime-boost vaccine regimens and to generate these or other immune responses that confer protection. Trial registration: South African National Clinical Trials Register (SANCTR number: DOH-27-0215-4796) and ClinicalTrials.gov (NCT02404311).

PLOS Global Public HealthVol. 4(9)
National Health Laboratory Service (ZA), South African Medical Research Council (ZA), National Institutes of Health (US), Desmond Tutu HIV Foundation (ZA), University of Cape Town (ZA), Duke University (US), University of the Witwatersrand (ZA), University of Washington (US), Centre for the AIDS Programme of Research in South Africa (ZA), Fred Hutch Cancer Center (US), GlaxoSmithKline (Belgium) (BE), Sanofi (United States) (US), Aurum Institute (ZA), Africa Health Research Institute (ZA), Integrative Medicine Institute (US), National Institute of Allergy and Infectious Diseases (US), Duke University Health System (US), Perinatal HIV Research Unit (ZA)
Bill and Melinda Gates Foundation, GlaxoSmithKline, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Public Health Service, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 85%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
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