PMID- 26180102
OWN - NLM
STAT- MEDLINE
DCOM- 20160426
LR  - 20181113
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 7
IP  - 296
DP  - 2015 Jul 15
TI  - HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 
      acquisition.
PG  - 296ra112
LID - 10.1126/scitranslmed.aab4005 [doi]
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.
CI  - Copyright (c) 2015, American Association for the Advancement of Science.
FAU - Prentice, Heather A
AU  - Prentice HA
AD  - 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.
FAU - Tomaras, Georgia D
AU  - Tomaras GD
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 
      27710, USA.
FAU - Geraghty, Daniel E
AU  - Geraghty DE
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 
      98109, USA.
FAU - Apps, Richard
AU  - Apps R
AD  - Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer 
      Research, Frederick, MD 21702, USA.
FAU - Fong, Youyi
AU  - Fong Y
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109, USA.
FAU - Ehrenberg, Philip K
AU  - Ehrenberg PK
AD  - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 
      Silver Spring, MD 20910, USA.
FAU - Rolland, Morgane
AU  - Rolland M
AD  - 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.
FAU - Kijak, Gustavo H
AU  - Kijak GH
AD  - 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.
FAU - Krebs, Shelly J
AU  - Krebs SJ
AD  - 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.
FAU - Nelson, Wyatt
AU  - Nelson W
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 
      98109, USA.
FAU - DeCamp, Allan
AU  - DeCamp A
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109, USA.
FAU - Shen, Xiaoying
AU  - Shen X
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 
      27710, USA.
FAU - Yates, Nicole L
AU  - Yates NL
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 
      27710, USA.
FAU - Zolla-Pazner, Susan
AU  - Zolla-Pazner S
AD  - Veterans Affairs New York Harbor Healthcare System and the Department of 
      Pathology, New York University School of Medicine, New York, NY 10016, USA.
FAU - Nitayaphan, Sorachai
AU  - Nitayaphan S
AD  - Department of Retrovirology, U.S. Army Medical Component, Armed Forces Research 
      Institute Medical Sciences, Bangkok 10400, Thailand.
FAU - Rerks-Ngarm, Supachai
AU  - Rerks-Ngarm S
AD  - Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, 
      Thailand.
FAU - Kaewkungwal, Jaranit
AU  - Kaewkungwal J
AD  - Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), 
      Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
FAU - Pitisuttithum, Punnee
AU  - Pitisuttithum P
AD  - Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok 
      10400, Thailand.
FAU - Ferrari, Guido
AU  - Ferrari G
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 
      27710, USA.
FAU - McElrath, M Juliana
AU  - McElrath MJ
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109, USA.
FAU - Montefiori, David C
AU  - Montefiori DC
AD  - Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 
      27710, USA.
FAU - Bailer, Robert T
AU  - Bailer RT
AD  - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, 
      National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Koup, Richard A
AU  - Koup RA
AD  - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, 
      National Institutes of Health, Bethesda, MD 20892, USA.
FAU - O'Connell, Robert J
AU  - O'Connell RJ
AD  - Department of Retrovirology, U.S. Army Medical Component, Armed Forces Research 
      Institute Medical Sciences, Bangkok 10400, Thailand.
FAU - Robb, Merlin L
AU  - Robb ML
AD  - 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.
FAU - Michael, Nelson L
AU  - Michael NL
AD  - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 
      Silver Spring, MD 20910, USA.
FAU - Gilbert, Peter B
AU  - Gilbert PB
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, WA 98109, USA.
FAU - Kim, Jerome H
AU  - Kim JH
AD  - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 
      Silver Spring, MD 20910, USA.
FAU - Thomas, Rasmi
AU  - Thomas R
AD  - 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.
LA  - eng
GR  - AI064518/AI/NIAID NIH HHS/United States
GR  - P01 AI100151/AI/NIAID NIH HHS/United States
GR  - P01 AI030731/AI/NIAID NIH HHS/United States
GR  - UM1 AI068618/AI/NIAID NIH HHS/United States
GR  - UM1 AI068635/AI/NIAID NIH HHS/United States
GR  - P30 AI064518/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (AIDS Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (HIV Antibodies)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPB1 antigen)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - AIDS Vaccines
MH  - Alleles
MH  - Antibody Formation/immunology
MH  - Epitopes/chemistry
MH  - Genotype
MH  - HIV Antibodies/immunology
MH  - HIV Envelope Protein gp120/*immunology/metabolism
MH  - HIV Infections/*genetics/*immunology
MH  - HIV-1
MH  - HLA-DP beta-Chains/*genetics
MH  - HLA-DQ beta-Chains/*genetics
MH  - *Histocompatibility Antigens Class II
MH  - Humans
MH  - Immunoglobulin A/immunology
MH  - Immunoglobulin G/immunology
MH  - Multivariate Analysis
MH  - Protein Structure, Tertiary
MH  - Regression Analysis
PMC - PMC4911012
MID - NIHMS792334
COIS- Competing interests: The authors declare that they have no competing interests.
EDAT- 2015/07/17 06:00
MHDA- 2016/04/27 06:00
PMCR- 2016/06/16
CRDT- 2015/07/17 06:00
PHST- 2015/07/17 06:00 [entrez]
PHST- 2015/07/17 06:00 [pubmed]
PHST- 2016/04/27 06:00 [medline]
PHST- 2016/06/16 00:00 [pmc-release]
AID - 7/296/296ra112 [pii]
AID - 10.1126/scitranslmed.aab4005 [doi]
PST - ppublish
SO  - Sci Transl Med. 2015 Jul 15;7(296):296ra112. doi: 10.1126/scitranslmed.aab4005.