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HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.

  • Yates NL Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • deCamp AC Vaccine and Infectious Disease Division and Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Korber BT Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
  • Liao HX Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Irene C Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
  • Pinter A Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
  • Peacock J Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Harris LJ Vaccine and Infectious Disease Division and Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Sawant S Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Hraber P Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
  • Shen X Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Rerks-Ngarm S Thailand Ministry of Public Health, Department of Disease Control, Bangkok, Thailand.
  • Pitisuttithum P Vaccine Trial Center, Mahidol University, Bangkok, Thailand.
  • Nitayapan S Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
  • Berman PW Department of Biomedical Engineering, University of California, Santa Cruz, California, USA.
  • Robb ML Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA and the U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
  • Pantaleo G Service of Immunology and Allergy, Service of Infectious Diseases, Department of Medicine and Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
  • Zolla-Pazner S Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Haynes BF Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Alam SM Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Montefiori DC Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
  • Tomaras GD Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA gdt@duke.edu.
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  • 2018-02-02
Published in:
  • Journal of virology. - 2018
HIV-1
antibody
antigenicity
diversity
durability
humoral immunity
vaccine
AIDS Vaccines
Animals
Genetic Variation
HIV Antibodies
HIV Envelope Protein gp120
HIV Infections
HIV-1
Humans
Macaca mulatta
English 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.IMPORTANCE The path toward an efficacious HIV-1 vaccine will require characterization of vaccine-induced immunity that can recognize and target the highly genetically diverse virus envelope glycoproteins. Antibodies that target the envelope glycoproteins, including diverse sequences within the first and second hypervariable regions (V1V2) of gp120, were identified as correlates of risk for the one partially efficacious HIV-1 vaccine. To build upon this discovery, we experimentally and computationally evaluated humoral responses to define envelope glycoproteins representative of the antigenic diversity of HIV globally. These diverse envelope antigens distinguished binding antibody breadth and durability among vaccine candidates, thus providing insights for advancing the most promising HIV-1 vaccine candidates.
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  • English
Open access status
hybrid
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https://sonar.ch/global/documents/78880
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