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.
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20818, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Prentice
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
authors.affiliation: Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Apps
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Fong
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Ehrenberg
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20818, USA.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20818, USA.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Kijak
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20818, USA.
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Krebs
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Nelson
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: DeCamp
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yates
authors.affiliation: Veterans Affairs New York Harbor Healthcare System and the Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.affiliation: Department of Retrovirology, U.S. Army Medical Component, Armed Forces Research Institute Medical Sciences, Bangkok 10400, Thailand.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand.
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Department of Retrovirology, U.S. Army Medical Component, Armed Forces Research Institute Medical Sciences, Bangkok 10400, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20818, USA.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20818, USA. rthomas@hivresearch.org.
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
mesh_terms: D016915:AIDS Vaccines; D000483:Alleles; D000917:Antibody Formation / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1; D059868:HLA-DP beta-Chains / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015999:Multivariate Analysis; D017434:Protein Structure, Tertiary; D012044:Regression Analysis
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G