Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk

Zoe Moodie; One Dintwe; Sheetal Sawant; Doug Grove; Yunda Huang; Holly Janes; Jack Heptinstall; Faatima Laher Omar; Kristen Cohen; Stephen C De Rosa; Lu Zhang; Nicole L Yates; Marcella Sarzotti-Kelsoe; Kelly E Seaton; Fatima Laher; Linda Gail Bekker; Mookho Malahleha; Craig Innes; Sheetal Kassim; Nivashnee Naicker; Vaneshree Govender; Modulakgotla Sebe; Nishanta Singh; Philip Kotze; Erica Lazarus; Maphoshane Nchabeleng; Amy M Ward; William Brumskine; Thozama Dubula; April K Randhawa; Nicole Grunenberg; John Hural; Jia Jin Kee; David Benkeser; Yutong Jin; Lindsay N Carpp; Mary Allen; Patricia D'Souza; James Tartaglia; Carlos A DiazGranados; Marguerite Koutsoukos; Peter B Gilbert; James G Kublin; Lawrence Corey; Erica Andersen-Nissen; Glenda E Gray; Georgia D Tomaras; M Juliana McElrath

doi:10.1093/infdis/jiac260

Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk

J Infect Dis. 2022 Aug 24;226(2):246-257. doi: 10.1093/infdis/jiac260.

Authors

Zoe Moodie¹, One Dintwe^{1

2}, Sheetal Sawant^{3

4}, Doug Grove¹, Yunda Huang^{1

5

6}, Holly Janes^{1

7}, Jack Heptinstall^{3

4}, Faatima Laher Omar², Kristen Cohen¹, Stephen C De Rosa^{1

8}, Lu Zhang^{3

4}, Nicole L Yates^{3

4}, Marcella Sarzotti-Kelsoe^{4

9}, Kelly E Seaton^{3

4}, Fatima Laher¹⁰, Linda Gail Bekker¹¹, Mookho Malahleha^{12

13}, Craig Innes¹⁴, Sheetal Kassim¹¹, Nivashnee Naicker¹⁵, Vaneshree Govender¹⁶, Modulakgotla Sebe¹⁷, Nishanta Singh¹⁶, Philip Kotze¹⁸, Erica Lazarus¹⁰, Maphoshane Nchabeleng¹⁹, Amy M Ward^{20

21}, William Brumskine²², Thozama Dubula²³, April K Randhawa¹, Nicole Grunenberg¹, John Hural¹, Jia Jin Kee¹, David Benkeser²⁴, Yutong Jin²⁴, Lindsay N Carpp¹, Mary Allen²⁵, Patricia D'Souza²⁵, James Tartaglia²⁶, Carlos A DiazGranados²⁶, Marguerite Koutsoukos²⁷, Peter B Gilbert^{1

6

7}, James G Kublin¹, Lawrence Corey^{1

8}, Erica Andersen-Nissen^{1

2}, Glenda E Gray^{10

16}, Georgia D Tomaras^{3

4

9

28}, M Juliana McElrath^{1

29}

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
² Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa.
³ Center for Human Systems Immunology, Duke University, Durham, North Carolina, USA.
⁴ Department of Surgery, Duke University, Durham, North Carolina, USA.
⁵ Department of Global Health, University of Washington, Seattle, Washington, USA.
⁶ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
⁷ Department of Biostatistics, University of Washington, Seattle, Washington, USA.
⁸ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
⁹ Department of Immunology, Duke University, Durham, North Carolina, USA.
¹⁰ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
¹¹ Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.
¹² Setshaba Research Centre, Soshanguve, South Africa.
¹³ Synergy Biomed Research Institute, East London, South Africa.
¹⁴ The Aurum Institute, Klerksdorp, South Africa.
¹⁵ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
¹⁶ South African Medical Research Council, Durban, South Africa.
¹⁷ Aurum Institute, Tembisa, South Africa.
¹⁸ Qhakaza Mbokodo Research Centre, Ladysmith, South Africa.
¹⁹ Mecru Clinical Research Unit, Sefako Makgatho Health Sciences University, Pretoria, South Africa.
²⁰ Department of Medicine, University of Cape Town, Cape Town, South Africa.
²¹ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
²² Aurum Institute, Johannesburg, South Africa.
²³ Nelson Mandela Academic Clinical Research Unit and Department of Internal Medicine and Pharmacology, Walter Sisulu University, Mthatha, South Africa.
²⁴ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
²⁵ National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²⁶ Sanofi-Pasteur, Swiftwater, Pennsylvania, USA.
²⁷ GSK, Wavre, Belgium.
²⁸ Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA.
²⁹ Department of Medicine, University of Washington, Seattle, Washington, USA.

Abstract

Background: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition.

Methods: Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4+ T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition.

Results: The HVTN 702 Env-specific CD4+ T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; Pmag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4+ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40-0.49 per 1-SD increase in CD4+ T-cell endpoint).

Conclusions: HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4+ T cells with HIV-1 acquisition. Clinical Trials Registration . NCT02968849.

Keywords: HIV-1 vaccine; HVTN 702; RV144; T-cell immunogenicity; T-cell polyfunctionality; binding antibodies; correlates of risk; intracellular cytokine staining; vaccine efficacy trial; vaccine-induced immune response.

Publication types

Clinical Trial, Phase II
Clinical Trial, Phase III
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

AIDS Vaccines*
Female
HIV Antibodies
HIV Envelope Protein gp120
HIV Infections* / prevention & control
HIV Seropositivity*
HIV-1*
Humans
Immunoglobulin G
Male
South Africa

Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk

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