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

dc.contributor.author Shen, Xiaoying
dc.contributor.author Tomaras, Georgia
dc.contributor.author Haynes, Barton
dc.contributor.author Montefiori, David
dc.contributor.author Liao, Hua-Xin
dc.contributor.author Alam, Munir
dc.contributor.author Yates, Nicole L
dc.contributor.author deCamp, Allan C
dc.contributor.author Korber, Bette T
dc.contributor.author Irene, Carmela
dc.contributor.author Pinter, Abraham
dc.contributor.author Peacock, James
dc.contributor.author Harris, Linda J
dc.contributor.author Sawant, Sheetal
dc.contributor.author Hraber, Peter
dc.contributor.author Shen, Xiaoying
dc.contributor.author Rerks-Ngarm, Supachai
dc.contributor.author Pitisuttithum, Punnee
dc.contributor.author Nitayapan, Sorachai
dc.contributor.author Berman, Phillip W
dc.contributor.author Robb, Merlin L
dc.contributor.author Pantaleo, Giuseppe
dc.contributor.author Zolla-Pazner, Susan
dc.date.accessioned 2018-11-27T16:58:36Z
dc.date.available 2018-11-27T16:58:36Z
dc.date.issued 2018-04
dc.identifier JVI.01843-17
dc.identifier.issn 0022-538X
dc.identifier.issn 1098-5514
dc.identifier.uri https://hdl.handle.net/10161/17674
dc.description.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 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.
dc.language eng
dc.publisher AMER SOC MICROBIOLOGY
dc.relation.ispartof Journal of virology
dc.relation.isversionof 10.1128/JVI.01843-17
dc.subject Animals
dc.subject Macaca mulatta
dc.subject Humans
dc.subject HIV-1
dc.subject HIV Infections
dc.subject HIV Envelope Protein gp120
dc.subject AIDS Vaccines
dc.subject HIV Antibodies
dc.subject Genetic Variation
dc.title HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.
dc.type Journal article
dc.date.updated 2018-11-27T16:58:30Z
pubs.issue 8
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pathology
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Medicine
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Immunology
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke Global Health Institute
pubs.organisational-group University Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group Surgery
pubs.organisational-group Molecular Genetics and Microbiology
pubs.publication-status Published
pubs.volume 92
duke.contributor.orcid Shen, Xiaoying|0000-0001-8076-1931
duke.contributor.orcid Tomaras, Georgia|0000-0001-8076-1931
duke.contributor.orcid Montefiori, David|0000-0003-0856-6319


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