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 McElrath; David 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

doi:10.1126/scitranslmed.aab4005

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 journal › Article › peer-review

46 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 language	English
Article number	296ra112
Journal	Science Translational Medicine
Volume	7
Issue number	296
DOIs	https://doi.org/10.1126/scitranslmed.aab4005
State	Published - 15 Jul 2015
Externally published	Yes

Access to Document

10.1126/scitranslmed.aab4005

Cite this

Prentice, H. A., Tomaras, G. D., Geraghty, D. E., Apps, R., Fong, Y., Ehrenberg, P. K., Rolland, M., Kijak, G. H., Krebs, S. J., Nelson, W., DeCamp, A., Shen, X., Yates, N. L., Zolla-Pazner, S., Nitayaphan, S., Rerks-Ngarm, S., Kaewkungwal, J., Pitisuttithum, P., Ferrari, G., ... Thomas, R. (2015). HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Science Translational Medicine, 7(296), Article 296ra112. https://doi.org/10.1126/scitranslmed.aab4005

@article{ef62ba4487284ab58a94d7e34225c5d6,

title = "HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition",

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.",

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

year = "2015",

month = jul,

day = "15",

doi = "10.1126/scitranslmed.aab4005",

language = "English",

volume = "7",

journal = "Science Translational Medicine",

issn = "1946-6234",

number = "296",

}

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 2015, 'HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition', Science Translational Medicine, vol. 7, no. 296, 296ra112. https://doi.org/10.1126/scitranslmed.aab4005

TY - JOUR

T1 - HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition

AU - Prentice, Heather A.

AU - Tomaras, Georgia D.

AU - Geraghty, Daniel E.

AU - Apps, Richard

AU - Fong, Youyi

AU - Ehrenberg, Philip K.

AU - Rolland, Morgane

AU - Kijak, Gustavo H.

AU - Krebs, Shelly J.

AU - Nelson, Wyatt

AU - DeCamp, Allan

AU - Shen, Xiaoying

AU - Yates, Nicole L.

AU - Zolla-Pazner, Susan

AU - Nitayaphan, Sorachai

AU - Rerks-Ngarm, Supachai

AU - Kaewkungwal, Jaranit

AU - Pitisuttithum, Punnee

AU - Ferrari, Guido

AU - McElrath, M. Juliana

AU - Montefiori, David C.

AU - Bailer, Robert T.

AU - Koup, Richard A.

AU - O'Connell, Robert J.

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - Gilbert, Peter B.

AU - Kim, Jerome H.

AU - Thomas, Rasmi

PY - 2015/7/15

Y1 - 2015/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84937131006&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aab4005

DO - 10.1126/scitranslmed.aab4005

M3 - Article

C2 - 26180102

AN - SCOPUS:84937131006

SN - 1946-6234

VL - 7

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 296

M1 - 296ra112

ER -

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

Abstract

Access to Document

Fingerprint

Cite this