Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials

Nonhlanhla N Mkhize; Anna E J Yssel; Haajira Kaldine; Rebecca T van Dorsten; Amanda S Woodward Davis; Nicolas Beaume; David Matten; Bronwen Lambson; Tandile Modise; Prudence Kgagudi; Talita York; Dylan H Westfall; Elena E Giorgi; Bette Korber; Colin Anthony; Rutendo E Mapengo; Valerie Bekker; Elizabeth Domin; Amanda Eaton; Wenjie Deng; Allan DeCamp; Yunda Huang; Peter B Gilbert; Asanda Gwashu-Nyangiwe; Ruwayhida Thebus; Nonkululeko Ndabambi; Dieter Mielke; Nyaradzo Mgodi; Shelly Karuna; Srilatha Edupuganti; Michael S Seaman; Lawrence Corey; Myron S Cohen; John Hural; M Juliana McElrath; James I Mullins; David Montefiori; Penny L Moore; Carolyn Williamson; Lynn Morris

doi:10.1371/journal.ppat.1011469

Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials

PLoS Pathog. 2023 Jun 29;19(6):e1011469. doi: 10.1371/journal.ppat.1011469. eCollection 2023 Jun.

Authors

Nonhlanhla N Mkhize^{1

2}, Anna E J Yssel³, Haajira Kaldine^{1

2}, Rebecca T van Dorsten^{1

2

4}, Amanda S Woodward Davis⁵, Nicolas Beaume³, David Matten³, Bronwen Lambson^{1

2}, Tandile Modise^{1

2}, Prudence Kgagudi^{1

2}, Talita York³, Dylan H Westfall⁶, Elena E Giorgi⁵, Bette Korber⁷, Colin Anthony³, Rutendo E Mapengo^{1

2}, Valerie Bekker¹, Elizabeth Domin⁸, Amanda Eaton⁸, Wenjie Deng⁶, Allan DeCamp⁵, Yunda Huang⁵, Peter B Gilbert⁵, Asanda Gwashu-Nyangiwe³, Ruwayhida Thebus³, Nonkululeko Ndabambi³, Dieter Mielke^{3

8}, Nyaradzo Mgodi⁹, Shelly Karuna⁵, Srilatha Edupuganti¹⁰, Michael S Seaman¹¹, Lawrence Corey^{5

12}, Myron S Cohen¹³, John Hural⁵, M Juliana McElrath⁵, James I Mullins⁶, David Montefiori⁸, Penny L Moore^{1

2

14}, Carolyn Williamson^{3

14

15}, Lynn Morris^{1

2

14}

Affiliations

¹ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
² SA MRC Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ Institute for Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁴ South African Medical Research Council Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences University of the Witwatersrand, Johannesburg, South Africa.
⁵ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America.
⁶ Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
⁷ Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
⁸ Department of Surgery, Duke University, Durham, North Carolina, United States of America.
⁹ University of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe.
¹⁰ Division of Infectious Diseases, Department of Medicine, Emory University, Decatur, Georgia, United States of America.
¹¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
¹² Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.
¹³ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North-Carolina, United States of America.
¹⁴ Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa.
¹⁵ National Health Laboratory Service, Cape Town, South Africa.

Abstract

The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10-1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998-2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses.

Copyright: © 2023 Mkhize et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
Broadly Neutralizing Antibodies
HIV Antibodies
HIV Infections*
HIV Seropositivity*
HIV-1*
Humans
Polysaccharides

Substances

HIV Antibodies
Broadly Neutralizing Antibodies
Antibodies, Neutralizing
Polysaccharides

Abstract

Publication types

MeSH terms

Substances

Grants and funding