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

Journal Article · · PLoS Pathogens
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  1. National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg (South Africa); University of the Witwatersrand, Johannesburg (South Africa)
  2. University of Cape Town (South Africa)
  3. Fred Hutchinson Cancer Center, Seattle, WA (United States)
  4. University of Washington, Seattle, WA (United States)
  5. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
  6. National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg (South Africa)
  7. Duke University, Durham, NC (United States)
  8. University of Cape Town (South Africa); Duke University, Durham, NC (United States)
  9. University of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare (Zimbabwe)
  10. Emory University, Decatur, GA (United States)
  11. Harvard Medical School, Boston, MA (United States)
  12. Fred Hutchinson Cancer Center, Seattle, WA (United States); University of Washington, Seattle, WA (United States)
  13. University of North Carolina at Chapel Hill, NC (United States)
  14. National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg (South Africa); University of the Witwatersrand, Johannesburg (South Africa); University of KwaZulu Natal, Durban (South Africa)
  15. University of Cape Town (South Africa); University of KwaZulu Natal, Durban (South Africa); National Health Laboratory Service, Cape Town (South Africa)
+ Show Author Affiliations
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.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
89233218CNA000001
OSTI ID:
2470537
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 6 Vol. 19; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
Antibodies
Chemical neutralization
Forecasting
HIV-1
Microbiology
Parasitology
Phylogenetic analysis
RNA sequencing
Sequence alignment
Viral vaccines
Virology