HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees
Abstract
Induction of broadly cross-reactive antiviral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to evaluate vaccine regimens for binding antibody breadth. In this study, we define unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability. Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder viruses with a tier 2 neutralization phenotype. Unique antigenicity was determined by nonredundancy (Spearman correlation), and antigens were clustered using partitioning around medoids (PAM) to identify antigen diversity. Cross-validation demonstrated that the PAM method was better than selection by reactivity and random selection. Analysis of vaccine-elicited V1V2 binding antibody in longitudinal samples from the RV144 clinical trial revealed the striking heterogeneity among individual vaccinees in maintaining durable responses. These data support the idea that a major goal for vaccine development is to improve antibody levels, breadth, and durability at the population level. Elucidating the level and durability of vaccine-elicited binding antibody breadth needed for protection is critical for the development of a globally efficaciousmore »
- Authors:
-
more »
- Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Medicine
- Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Statistical Center for HIV/AIDS Research and Prevention. Vaccine and Infectious Disease Division
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
- Rutgers Univ., Newark, NJ (United States). New Jersey Medical School. Public Health Research Inst.
- Thailand Ministry of Public Health, Bangkok (Thailand). Department of Disease Control
- Mahidol Univ., Bangkok (Thailand). Vaccine Trial Center
- Armed Forces Research Inst. of Medical Sciences, Bangkok (Thailand)
- Univ. of California, Santa Cruz, CA (United States). Dept. of Biomedical Engineering
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD (United States); Walter Reed Army Inst. of Research, Silver Spring, MD (United States). US Military HIV Research Program
- Univ. of Lusanne (Switzerland). Lausanne Univ. Hospital. Swiss Vaccine Research Inst. Dept. of Medicine. Service of Infecitous Diseases. Service of Immunology and Allergy
- Icahn School of Medicine at Mount Sinai, New York, NY (United States)
- Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Medicine; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Immunology
- Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Surgery
- Duke Univ., Durham, NC (United States). School of Medicine. Duke Human Vaccine Inst.; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Immunology; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Surgery; Duke Univ., Durham, NC (United States). School of Medicine. Dept. of Molecular Genetics and Microbiology
- Publication Date:
- Research Org.:
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1626074
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Virology
- Additional Journal Information:
- Journal Volume: 92; Journal Issue: 8; Journal ID: ISSN 0022-538X
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; virology; humoral immunity; antibody; antigenicity; vaccine; HIV-1; diversity; durability
Citation Formats
Yates, Nicole L., deCamp, Allan C., Korber, Bette T., Liao, Hua-Xin, Irene, Carmela, Pinter, Abraham, Peacock, James, Harris, Linda J., Sawant, Sheetal, Hraber, Peter, Shen, Xiaoying, Rerks-Ngarm, Supachai, Pitisuttithum, Punnee, Nitayapan, Sorachai, Berman, Phillip W., Robb, Merlin L., Pantaleo, Giuseppe, Zolla-Pazner, Susan, Haynes, Barton F., Alam, S. Munir, Montefiori, David C., and Tomaras, Georgia D. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. United States: N. p., 2018.
Web. doi:10.1128/jvi.01843-17.
Yates, Nicole L., deCamp, Allan C., Korber, Bette T., Liao, Hua-Xin, Irene, Carmela, Pinter, Abraham, Peacock, James, Harris, Linda J., Sawant, Sheetal, Hraber, Peter, Shen, Xiaoying, Rerks-Ngarm, Supachai, Pitisuttithum, Punnee, Nitayapan, Sorachai, Berman, Phillip W., Robb, Merlin L., Pantaleo, Giuseppe, Zolla-Pazner, Susan, Haynes, Barton F., Alam, S. Munir, Montefiori, David C., & Tomaras, Georgia D. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. United States. https://doi.org/10.1128/jvi.01843-17
Yates, Nicole L., deCamp, Allan C., Korber, Bette T., Liao, Hua-Xin, Irene, Carmela, Pinter, Abraham, Peacock, James, Harris, Linda J., Sawant, Sheetal, Hraber, Peter, Shen, Xiaoying, Rerks-Ngarm, Supachai, Pitisuttithum, Punnee, Nitayapan, Sorachai, Berman, Phillip W., Robb, Merlin L., Pantaleo, Giuseppe, Zolla-Pazner, Susan, Haynes, Barton F., Alam, S. Munir, Montefiori, David C., and Tomaras, Georgia D. Wed .
"HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees". United States. https://doi.org/10.1128/jvi.01843-17. https://www.osti.gov/servlets/purl/1626074.
@article{osti_1626074,
title = {HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees},
author = {Yates, Nicole L. and deCamp, Allan C. and Korber, Bette T. and Liao, Hua-Xin and Irene, Carmela and Pinter, Abraham and Peacock, James and Harris, Linda J. and Sawant, Sheetal and Hraber, Peter and Shen, Xiaoying and Rerks-Ngarm, Supachai and Pitisuttithum, Punnee and Nitayapan, Sorachai and Berman, Phillip W. and Robb, Merlin L. and Pantaleo, Giuseppe and Zolla-Pazner, Susan and Haynes, Barton F. and Alam, S. Munir and Montefiori, David C. and Tomaras, Georgia D.},
abstractNote = {Induction of broadly cross-reactive antiviral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to evaluate vaccine regimens for binding antibody breadth. In this study, we define unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability. Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder viruses with a tier 2 neutralization phenotype. Unique antigenicity was determined by nonredundancy (Spearman correlation), and antigens were clustered using partitioning around medoids (PAM) to identify antigen diversity. Cross-validation demonstrated that the PAM method was better than selection by reactivity and random selection. Analysis of vaccine-elicited V1V2 binding antibody in longitudinal samples from the RV144 clinical trial revealed the striking heterogeneity among individual vaccinees in maintaining durable responses. These data support the idea that a major goal for vaccine development is to improve antibody levels, breadth, and durability at the population level. Elucidating the level and durability of vaccine-elicited binding antibody breadth needed for protection is critical for the development of a globally efficacious HIV vaccine.},
doi = {10.1128/jvi.01843-17},
journal = {Journal of Virology},
number = 8,
volume = 92,
place = {United States},
year = {Wed Mar 28 00:00:00 EDT 2018},
month = {Wed Mar 28 00:00:00 EDT 2018}
}
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