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

Publication ,  Journal Article
Yates, NL; deCamp, AC; Korber, BT; Liao, H-X; Irene, C; Pinter, A; Peacock, J; Harris, LJ; Sawant, S; Hraber, P; Shen, X; Rerks-Ngarm, S ...
Published in: J Virol
April 15, 2018

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.

Duke Scholars

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

April 15, 2018

Volume

92

Issue

8

Location

United States

Related Subject Headings

  • Virology
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Genetic Variation
  • Animals
  • AIDS Vaccines
 

Citation

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Chicago
ICMJE
MLA
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Yates, N. L., deCamp, A. C., Korber, B. T., Liao, H.-X., Irene, C., Pinter, A., … Tomaras, G. D. (2018). HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J Virol, 92(8). https://doi.org/10.1128/JVI.01843-17
Yates, Nicole L., Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, et al. “HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.J Virol 92, no. 8 (April 15, 2018). https://doi.org/10.1128/JVI.01843-17.
Yates NL, deCamp AC, Korber BT, Liao H-X, Irene C, Pinter A, et al. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J Virol. 2018 Apr 15;92(8).
Yates, Nicole L., et al. “HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees.J Virol, vol. 92, no. 8, Apr. 2018. Pubmed, doi:10.1128/JVI.01843-17.
Yates NL, deCamp AC, Korber BT, Liao H-X, Irene C, Pinter A, Peacock J, Harris LJ, Sawant S, Hraber P, Shen X, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Berman PW, Robb ML, Pantaleo G, Zolla-Pazner S, Haynes BF, Alam SM, Montefiori DC, Tomaras GD. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J Virol. 2018 Apr 15;92(8).

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

April 15, 2018

Volume

92

Issue

8

Location

United States

Related Subject Headings

  • Virology
  • Macaca mulatta
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Genetic Variation
  • Animals
  • AIDS Vaccines