Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization
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- Univ. of Cape Town (South Africa). National Health Lab. Service (NHLS). Inst. of Infectious Diseases and Molecular Medicine. Division of Medical Virology
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). New Mexico Consortium
- Beth Israel Deaconess Medical Center, Boston, MA (United States)
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery
- Botswana-Harvard AIDS Inst. Partnership, Gaborone (Botswana)
- National Inst. for Communicable Disease (NICD), Johannesburg (South Africa). NHLS; Univ. of Witwatersrand, Johannesburg (South Africa)
- National Inst. for Communicable Disease (NICD), Johannesburg (South Africa). NHLS; Univ. of Witwatersrand, Johannesburg (South Africa); Univ. of KwaZulu-Natal, Durban (South Africa). Centre for the AIDS Programme of Research in South Africa (CAPRISA)
- Univ. of Witwatersrand, Johannesburg (South Africa). South African medical Research Council. Faculty of Health Sciences. Perinatal HIV Research Unit
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Vaccine and Infectious Disease Division
- South African National Blood Service, Weltevreden Park (South Africa)
- Univ. of Cape Town (South Africa). Inst. of Infectious Diseases and Molecular Medicine. Dept. of Medicine. Desmond Tutu HIV Centre
- Klinikum Univ. of Munich (Gremany). German Center for Infection Research (DZIF). Dept. for Infectious Diseases and Tropical Medicine
- NIMR-Mbeya Medical Research Center, Mbeya (Tanzania)
- Botswana-Harvard AIDS Institute Partnership, Gaborone (Botswana)
- Walter Reed Army Institute of Research, Silver Spring, MD (United States). US Military HIV Research Program
- Univ. of KwaZulu-Natal, Durban (South Africa). Centre for the AIDS Programme of Research in South Africa (CAPRISA)
- Walter Reed Army Institute of Research, Silver Spring, MD (United States). US Military HIV Research Program; International Vaccine Inst., Seoul (Republic of Korea)
- Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine
- Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Biochemistry and Biophysics
- Univ. of Cape Town (South Africa). National Health Lab. Service (NHLS). Inst. of Infectious Diseases and Molecular Medicine. Division of Medical Virology; Univ. of KwaZulu-Natal, Durban (South Africa). Centre for the AIDS Programme of Research in South Africa (CAPRISA)
The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clade C epidemic regions in southern Africa are imminent; passive administration of the monoclonal antibody VRC01, and active immunization with a clade C modified RV144-like vaccines. We have created a large representative panel of C clade viruses to enable assessment of antibody responses to vaccines and natural infection in Southern Africa, and we investigated the genotypic and neutralization properties of recently transmitted clade C viruses to determine how viral diversity impacted antibody recognition. We further explore the implications of these findings for the potential effectiveness of these trials. A panel of 200 HIV-1 Envelope pseudoviruses was constructed from clade C viruses collected within the first 100 days following infection. Viruses collected pre-seroconversion were significantly more resistant to serum neutralization compared to post-seroconversion viruses (p = 0.001). Over 13 years of the study as the epidemic matured, HIV-1 diversified (p = 0.0009) and became more neutralization resistant to monoclonal antibodies VRC01, PG9 and 4E10. When tested at therapeutic levels (10ug/ml), VRC01 only neutralized 80% of viruses in the panel, although it did exhibit potent neutralization activity against sensitive viruses (IC50 titres of 0.42 μg/ml). The Gp120 amino acid similarity between the clade C panel and candidate C-clade vaccine protein boosts (Ce1086 and TV1) was 77%, which is 8% more distant than between CRF01_AE viruses and the RV144 CRF01_AE immunogen. Furthermore, two vaccine signature sites, K169 in V2 and I307 in V3, associated with reduced infection risk in RV144, occurred less frequently in clade C panel viruses than in CRF01_AE viruses from Thailand. Increased resistance of pre-seroconversion viruses and evidence of antigenic drift highlights the value of using panels of very recently transmitted viruses and suggests that interventions may need to be modified over time to track the changing epidemic. Furthermore, high divergence such as that observed in the older clade C epidemic in southern Africa may impact vaccine efficacy, although the correlates of infection risk are yet to be defined in the clade C setting. Findings from this study of acute/early clade C viruses will aid vaccine development, and enable identification of new broad and potent antibodies to combat the HIV-1 C-clade epidemic in southern Africa.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- Grant/Contract Number:
- AC52-06NA25396
- OSTI ID:
- 1627912
- Journal Information:
- PLoS Pathogens, Vol. 12, Issue 7; ISSN 1553-7374
- Publisher:
- Public Library of ScienceCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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