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

Details

Serval ID
serval:BIB_7D182EB82921
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.
Journal
Journal of virology
Author(s)
Yates N.L., deCamp A.C., Korber B.T., Liao H.X., Irene C., Pinter A., Peacock J., Harris L.J., Sawant S., Hraber P., Shen X., Rerks-Ngarm S., Pitisuttithum P., Nitayapan S., Berman P.W., Robb M.L., Pantaleo G., Zolla-Pazner S., Haynes B.F., Alam S.M., Montefiori D.C., Tomaras G.D.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
15/04/2018
Peer-reviewed
Oui
Volume
92
Number
8
Pages
e01843-17
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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. <b>IMPORTANCE</b> 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.

Keywords
AIDS Vaccines/genetics, AIDS Vaccines/immunology, Animals, Genetic Variation/immunology, HIV Antibodies/immunology, HIV Envelope Protein gp120/genetics, HIV Envelope Protein gp120/immunology, HIV Infections/genetics, HIV Infections/immunology, HIV-1/genetics, HIV-1/immunology, Humans, Macaca mulatta, HIV-1, antibody, antigenicity, diversity, durability, humoral immunity, vaccine
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2018 19:42
Last modification date
20/08/2019 14:38
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