title: Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection.
abstract: In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00223080.
authors: Department of Veterans Affairs New York Harbor Healthcare System, New York, New York, United States of America ; New York University School of Medicine, New York, New York, United States of America.
authors: Susan
authors: S
authors: Zolla-Pazner
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Allan
authors: A
authors: deCamp
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Peter B
authors: PB
authors: Gilbert
authors: New York University School of Medicine, New York, New York, United States of America.
authors: Constance
authors: C
authors: Williams
authors: Duke University, Durham, North Carolina, United States of America.
authors: Nicole L
authors: NL
authors: Yates
authors: Duke University, Durham, North Carolina, United States of America.
authors: William T
authors: WT
authors: Williams
authors: Duke University, Durham, North Carolina, United States of America.
authors: Robert
authors: R
authors: Howington
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Youyi
authors: Y
authors: Fong
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Daryl E
authors: DE
authors: Morris
authors: Duke University, Durham, North Carolina, United States of America.
authors: Kelly A
authors: KA
authors: Soderberg
authors: Public Health Research Institute, University of Medicine and Dentistry, Newark, New Jersey, United States of America.
authors: Carmela
authors: C
authors: Irene
authors: Public Health Research Institute, University of Medicine and Dentistry, Newark, New Jersey, United States of America.
authors: Charles
authors: C
authors: Reichman
authors: Public Health Research Institute, University of Medicine and Dentistry, Newark, New Jersey, United States of America.
authors: Abraham
authors: A
authors: Pinter
authors: Duke University, Durham, North Carolina, United States of America.
authors: Robert
authors: R
authors: Parks
authors: Faculty of Tropical Medicine, Mahidol, Thailand.
authors: Punnee
authors: P
authors: Pitisuttithum
authors: Faculty of Tropical Medicine, Mahidol, Thailand.
authors: Jaranit
authors: J
authors: Kaewkungwal
authors: Ministry of Public Health, Bangkok, Thailand.
authors: Supachai
authors: S
authors: Rerks-Ngarm
authors: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors: Sorachai
authors: S
authors: Nitayaphan
authors: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Charla
authors: C
authors: Andrews
authors: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Robert J
authors: RJ
authors: O'Connell
authors: Virology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Zhi-yong
authors: ZY
authors: Yang
authors: Virology Laboratory, Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Gary J
authors: GJ
authors: Nabel
authors: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Jerome H
authors: JH
authors: Kim
authors: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors: Nelson L
authors: NL
authors: Michael
authors: Duke University, Durham, North Carolina, United States of America.
authors: David C
authors: DC
authors: Montefiori
authors: Duke University, Durham, North Carolina, United States of America.
authors: Hua-Xin
authors: HX
authors: Liao
authors: Duke University, Durham, North Carolina, United States of America.
authors: Barton F
authors: BF
authors: Haynes
authors: Duke University, Durham, North Carolina, United States of America.
authors: Georgia D
authors: GD
authors: Tomaras
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D010919:Placebos; D012307:Risk Factors; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D010919:Placebos; C514793:gp120 protein, Human immunodeficiency virus 1