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Title: Comparison of antibody responses induced by RV144, VAX003, and VAX004 vaccination regimens
Authors: Chitraporn Karnasuta
Siriwat Akapirat
Sirinan Madnote
Hathairat Savadsuk
Jiraporn Puangkaew
Surawach Rittiroongrad
Supachai Rerks-Ngarm
Sorachai Nitayaphan
Punnee Pitisuttithum
Jaranit Kaewkungwal
James Tartaglia
Faruk Sinangil
Donald P. Francis
Merlin L. Robb
Mark S. De Souza
Nelson L. Michael
Jean Louis Excler
Jerome H. Kim
Robert J. O'connell
Nicos Karasavvas
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
Sanofi Pasteur
Global Solutions for Infectious Diseases
Walter Reed Army Institute of Research
Thai Red Cross AIDS Research Centre
International Vaccine Institute, Seoul
Keywords: Immunology and Microbiology
Issue Date: 1-May-2017
Citation: AIDS Research and Human Retroviruses. Vol.33, No.5 (2017), 410-423
Abstract: © 2017, Mary Ann Liebert, Inc. 2017. 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.
ISSN: 19318405
Appears in Collections:Scopus 2016-2017

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