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

Heather A. Prentice, Georgia D. Tomaras, Daniel E. Geraghty, Richard Apps, Youyi Fong, Philip K. Ehrenberg, Morgane Rolland, Gustavo H. Kijak, Shelly J. Krebs, Wyatt Nelson, Allan DeCamp, Xiaoying Shen, Nicole L. Yates, Susan Zolla-Pazner, Sorachai Nitayaphan, Supachai Rerks-Ngarm, Jaranit Kaewkungwal, Punnee Pitisuttithum, Guido Ferrari, M. Juliana McElrathDavid C. Montefiori, Robert T. Bailer, Richard A. Koup, Robert J. O'Connell, Merlin L. Robb, Nelson L. Michael, Peter B. Gilbert, Jerome H. Kim, Rasmi Thomas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish
Article number296ra112
JournalScience Translational Medicine
Volume7
Issue number296
DOIs
StatePublished - 15 Jul 2015
Externally publishedYes

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