title: Comparison of Antibody Responses Induced by RV144, VAX003, and VAX004 Vaccination Regimens.
abstract: The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens, and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and Cyclic V2 (CycV2) and CycV3 peptides and gp70 V1 V2 scaffolds in these 3 HIV vaccine trials. After two protein immunizations, IgG responses to 92TH023 gp120 (contained in ALVAC-HIV vaccine) were significantly higher in RV144 but responses to other Env were higher in the VAX trials lacking ALVAC-HIV. IgG responses declined significantly between vaccinations. All trials induced antibodies to gp70 V1 V2 but VAX004 responses to 92TH023 gp70 V1 V2 were weak. All CycV2 responses were undetectable in VAX004 while 92TH023 gp70 V1 V2 was detected in both RV144 and VAX003 but MN CycV2 was detected only in VAX003. Multiple protein vaccinations in VAX trials did not improve magnitude or durability of V1 V2 and CycV2 antibodies. Herpes simplex virus glycoprotein D (gD) peptide at the N terminus of AIDSVAX®B/E and B/B gp120 proteins induced antibodies in all trials, although significantly higher in VAX trials. gD peptide induced IgA, IgG1, IgG2, and IgG3 but not IgG4. Multiple protein vaccinations decreased IgG3 and increased IgG4 changing subclass contribution to total IgG. Although confounded by different modes of HIV transmission, higher Env-specific IgA and IgG4 binding antibodies induced in the VAX trials compared to RV144 raises the hypothesis that these differences may have contributed to different vaccine efficacy results.
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Chitraporn
authors.initials: C
authors.lastname: Karnasuta
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Siriwat
authors.initials: S
authors.lastname: Akapirat
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Sirinan
authors.initials: S
authors.lastname: Madnote
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Hathairat
authors.initials: H
authors.lastname: Savadsuk
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Puangkaew
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Surawach
authors.initials: S
authors.lastname: Rittiroongrad
authors.affiliation: 2 Department of Disease Control, Ministry of Public Health , Nonthaburi, Thailand .
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: 3 Royal Thai Army , AFRIMS, Bangkok, Thailand .
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: 4 Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand .
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: 5 Center of Excellence for Biomedical and Public Health Informatics, Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand .
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: 6 Sanofi Pasteur , Swiftwater, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Tartaglia
authors.affiliation: 7 Global Solutions for Infectious Diseases (GSID) , South San Francisco, California.
authors.forename: Faruk
authors.initials: F
authors.lastname: Sinangil
authors.affiliation: 7 Global Solutions for Infectious Diseases (GSID) , South San Francisco, California.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Francis
authors.affiliation: 8 U.S. Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.|9 Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: 10 The Thai Red Cross AIDS Research Centre , Bangkok, Thailand .
authors.forename: Mark S
authors.initials: MS
authors.lastname: de Souza
authors.affiliation: 8 U.S. Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: 11 International Vaccine Institute , Seoul, Republic of Korea.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
authors.affiliation: 11 International Vaccine Institute , Seoul, Republic of Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.affiliation: 1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .|12 Viral Diseases Branch, Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Nicos
authors.initials: N
authors.lastname: Karasavvas
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000917:Antibody Formation; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D014838:Volunteers; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: HIV vaccines; HSV; IgG; IgG subclasses IgA; RV144; V1 V2; V2; V3; VAX003; VAX004; antibodies; gp120