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-Reference-Cited by-同舟云学术

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

Published:2022-06-27 Issue:2 Volume:226 Page:246-257
ISSN:0022-1899
Container-title:The Journal of Infectious Diseases
language:en
Short-container-title:

Author:

Moodie Zoe¹^ORCID,Dintwe One¹²,Sawant Sheetal³⁴,Grove Doug¹,Huang Yunda¹⁵⁶,Janes Holly¹⁷^ORCID,Heptinstall Jack³⁴,Omar Faatima Laher²,Cohen Kristen¹,De Rosa Stephen C¹⁸,Zhang Lu³⁴,Yates Nicole L³⁴,Sarzotti-Kelsoe Marcella⁴⁹,Seaton Kelly E³⁴,Laher Fatima¹⁰,Bekker Linda Gail¹¹,Malahleha Mookho¹²¹³,Innes Craig¹⁴,Kassim Sheetal¹¹,Naicker Nivashnee¹⁵,Govender Vaneshree¹⁶,Sebe Modulakgotla¹⁷,Singh Nishanta¹⁶,Kotze Philip¹⁸,Lazarus Erica¹⁰,Nchabeleng Maphoshane¹⁹,Ward Amy M²⁰²¹,Brumskine William²²,Dubula Thozama²³,Randhawa April K¹,Grunenberg Nicole¹,Hural John¹,Kee Jia Jin¹,Benkeser David²⁴^ORCID,Jin Yutong²⁴,Carpp Lindsay N¹,Allen Mary²⁵,D’Souza Patricia²⁵,Tartaglia James²⁶,DiazGranados Carlos A²⁶,Koutsoukos Marguerite²⁷,Gilbert Peter B¹⁶⁷,Kublin James G¹,Corey Lawrence¹⁸,Andersen-Nissen Erica¹²,Gray Glenda E¹⁰¹⁶,Tomaras Georgia D³⁴⁹²⁸,McElrath M Juliana¹²⁹

Affiliation:

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

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.

Funder

NIH

National Institute of Allergy and Infectious Diseases

HIV Vaccine Trials Network

HVTN Statistical Data and Management Center

Fred Hutchinson Cancer Research Center

HVTN Laboratory Center

Center for AIDS Research, Duke University

Bill and Melinda Gates Foundation

Novartis Vaccines and Diagnostics

GlaxoSmithKline Biologicals SA

Publisher