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Title: HIV-1 envelope glycoproteins from diverse clades differentiate antibody responses and durability among vaccinees
Authors: Nicole L. Yates
Allan C. deCamp
Bette T. Korber
Hua Xin Liao
Carmela Irene
Abraham Pinter
James Peacock
Linda J. Harris
Sheetal Sawant
Peter Hraber
Xiaoying Shen
Supachai Rerks-Ngarm
Punnee Pitisuttithum
Sorachai Nitayapan
Phillip W. Berman
Merlin L. Robb
Giuseppe Pantaleo
Susan Zolla-Pazner
Barton F. Haynes
S. Munir Alam
David C. Montefiori
Georgia D. Tomaras
University of California, Santa Cruz
Centre Hospitalier Universitaire Vaudois
Jinan University
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Icahn School of Medicine at Mount Sinai
Walter Reed Army Institute of Research
Mahidol University
Los Alamos National Laboratory
Rutgers New Jersey Medical School
Duke University School of Medicine
Fred Hutchinson Cancer Research Center
Keywords: Agricultural and Biological Sciences;Immunology and Microbiology
Issue Date: 1-Apr-2018
Citation: Journal of Virology. Vol.92, No.8 (2018)
Abstract: © 2018 American Society for Microbiology. 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.
ISSN: 10985514
Appears in Collections:Scopus 2018

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