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Title: 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 » HIV vaccine.« less

Authors:
 [1];  [2];  [3];  [1];  [4];  [4];  [1];  [2];  [1]; ORCiD logo [3];  [1];  [5];  [6];  [7];  [8];  [9];  [10]; ORCiD logo [11];  [12];  [1] more »;  [13]; ORCiD logo [14] « less
  1. 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
  2. Fred Hutchinson Cancer Research Center, Seattle, WA (United States). Statistical Center for HIV/AIDS Research and Prevention. Vaccine and Infectious Disease Division
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
  4. Rutgers Univ., Newark, NJ (United States). New Jersey Medical School. Public Health Research Inst.
  5. Thailand Ministry of Public Health, Bangkok (Thailand). Department of Disease Control
  6. Mahidol Univ., Bangkok (Thailand). Vaccine Trial Center
  7. Armed Forces Research Inst. of Medical Sciences, Bangkok (Thailand)
  8. Univ. of California, Santa Cruz, CA (United States). Dept. of Biomedical Engineering
  9. 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
  10. Univ. of Lusanne (Switzerland). Lausanne Univ. Hospital. Swiss Vaccine Research Inst. Dept. of Medicine. Service of Infecitous Diseases. Service of Immunology and Allergy
  11. Icahn School of Medicine at Mount Sinai, New York, NY (United States)
  12. 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
  13. 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
  14. 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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