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Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.

Publication ,  Journal Article
Bonsignori, M; Pollara, J; Moody, MA; Alpert, MD; Chen, X; Hwang, K-K; Gilbert, PB; Huang, Y; Gurley, TC; Kozink, DM; Marshall, DJ; Tsao, C-Y ...
Published in: J Virol
November 2012

The ALVAC-HIV/AIDSVAX-B/E RV144 vaccine trial showed an estimated efficacy of 31%. RV144 secondary immune correlate analysis demonstrated that the combination of low plasma anti-HIV-1 Env IgA antibodies and high levels of antibody-dependent cellular cytotoxicity (ADCC) inversely correlate with infection risk. One hypothesis is that the observed protection in RV144 is partially due to ADCC-mediating antibodies. We found that the majority (73 to 90%) of a representative group of vaccinees displayed plasma ADCC activity, usually (96.2%) blocked by competition with the C1 region-specific A32 Fab fragment. Using memory B-cell cultures and antigen-specific B-cell sorting, we isolated 23 ADCC-mediating nonclonally related antibodies from 6 vaccine recipients. These antibodies targeted A32-blockable conformational epitopes (n = 19), a non-A32-blockable conformational epitope (n = 1), and the gp120 Env variable loops (n = 3). Fourteen antibodies mediated cross-clade target cell killing. ADCC-mediating antibodies displayed modest levels of V-heavy (VH) chain somatic mutation (0.5 to 1.5%) and also displayed a disproportionate usage of VH1 family genes (74%), a phenomenon recently described for CD4-binding site broadly neutralizing antibodies (bNAbs). Maximal ADCC activity of VH1 antibodies correlated with mutation frequency. The polyclonality and low mutation frequency of these VH1 antibodies reveal fundamental differences in the regulation and maturation of these ADCC-mediating responses compared to VH1 bNAbs.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 2012

Volume

86

Issue

21

Start / End Page

11521 / 11532

Location

United States

Related Subject Headings

  • Virology
  • Male
  • Humans
  • Human Experimentation
  • HIV-1
  • HIV Antibodies
  • Genes, Immunoglobulin Heavy Chain
  • Female
  • Antibody-Dependent Cell Cytotoxicity
  • AIDS Vaccines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bonsignori, M., Pollara, J., Moody, M. A., Alpert, M. D., Chen, X., Hwang, K.-K., … Haynes, B. F. (2012). Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J Virol, 86(21), 11521–11532. https://doi.org/10.1128/JVI.01023-12
Bonsignori, Mattia, Justin Pollara, M Anthony Moody, Michael D. Alpert, Xi Chen, Kwan-Ki Hwang, Peter B. Gilbert, et al. “Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.J Virol 86, no. 21 (November 2012): 11521–32. https://doi.org/10.1128/JVI.01023-12.
Bonsignori, Mattia, et al. “Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family.J Virol, vol. 86, no. 21, Nov. 2012, pp. 11521–32. Pubmed, doi:10.1128/JVI.01023-12.
Bonsignori M, Pollara J, Moody MA, Alpert MD, Chen X, Hwang K-K, Gilbert PB, Huang Y, Gurley TC, Kozink DM, Marshall DJ, Whitesides JF, Tsao C-Y, Kaewkungwal J, Nitayaphan S, Pitisuttithum P, Rerks-Ngarm S, Kim JH, Michael NL, Tomaras GD, Montefiori DC, Lewis GK, DeVico A, Evans DT, Ferrari G, Liao H-X, Haynes BF. Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J Virol. 2012 Nov;86(21):11521–11532.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 2012

Volume

86

Issue

21

Start / End Page

11521 / 11532

Location

United States

Related Subject Headings

  • Virology
  • Male
  • Humans
  • Human Experimentation
  • HIV-1
  • HIV Antibodies
  • Genes, Immunoglobulin Heavy Chain
  • Female
  • Antibody-Dependent Cell Cytotoxicity
  • AIDS Vaccines