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HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition.

Publication ,  Journal Article
Prentice, HA; Tomaras, GD; Geraghty, DE; Apps, R; Fong, Y; Ehrenberg, PK; Rolland, M; Kijak, GH; Krebs, SJ; Nelson, W; DeCamp, A; Shen, X ...
Published in: Sci Transl Med
July 15, 2015

In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II-restricted CD4(+) T cells are involved in antibody production, we tested whether HLA class II genotypes affected HIV-1-specific antibody levels and HIV-1 acquisition in 760 individuals. Indeed, antibody responses correlated with acquisition only in the presence of single host HLA alleles. Envelope (Env)-specific immunoglobulin A (IgA) antibodies were associated with increased risk of acquisition specifically in individuals with DQB1*06. IgG antibody responses to Env amino acid positions 120 to 204 were higher and were associated with decreased risk of acquisition and increased vaccine efficacy only in the presence of DPB1*13. Screening IgG responses to overlapping peptides spanning Env 120-204 and viral sequence analysis of infected individuals defined differences in vaccine response that were associated with the presence of DPB1*13 and could be responsible for the protection observed. Overall, the underlying genetic findings indicate that HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 trial.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

July 15, 2015

Volume

7

Issue

296

Start / End Page

296ra112

Location

United States

Related Subject Headings

  • Regression Analysis
  • Protein Structure, Tertiary
  • Multivariate Analysis
  • Immunoglobulin G
  • Immunoglobulin A
  • Humans
  • Histocompatibility Antigens Class II
  • HLA-DQ beta-Chains
  • HLA-DP beta-Chains
  • HIV-1
 

Citation

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Prentice, H. A., Tomaras, G. D., Geraghty, D. E., Apps, R., Fong, Y., Ehrenberg, P. K., … Thomas, R. (2015). HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Sci Transl Med, 7(296), 296ra112. https://doi.org/10.1126/scitranslmed.aab4005
Prentice, Heather A., Georgia D. Tomaras, Daniel E. Geraghty, Richard Apps, Youyi Fong, Philip K. Ehrenberg, Morgane Rolland, et al. “HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition.Sci Transl Med 7, no. 296 (July 15, 2015): 296ra112. https://doi.org/10.1126/scitranslmed.aab4005.
Prentice HA, Tomaras GD, Geraghty DE, Apps R, Fong Y, Ehrenberg PK, et al. HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Sci Transl Med. 2015 Jul 15;7(296):296ra112.
Prentice, Heather A., et al. “HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition.Sci Transl Med, vol. 7, no. 296, July 2015, p. 296ra112. Pubmed, doi:10.1126/scitranslmed.aab4005.
Prentice HA, Tomaras GD, Geraghty DE, Apps R, Fong Y, Ehrenberg PK, Rolland M, Kijak GH, Krebs SJ, Nelson W, DeCamp A, Shen X, Yates NL, Zolla-Pazner S, Nitayaphan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Ferrari G, McElrath MJ, Montefiori DC, Bailer RT, Koup RA, O’Connell RJ, Robb ML, Michael NL, Gilbert PB, Kim JH, Thomas R. HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Sci Transl Med. 2015 Jul 15;7(296):296ra112.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

July 15, 2015

Volume

7

Issue

296

Start / End Page

296ra112

Location

United States

Related Subject Headings

  • Regression Analysis
  • Protein Structure, Tertiary
  • Multivariate Analysis
  • Immunoglobulin G
  • Immunoglobulin A
  • Humans
  • Histocompatibility Antigens Class II
  • HLA-DQ beta-Chains
  • HLA-DP beta-Chains
  • HIV-1