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AIDS Res Hum Retroviruses. 2017 May;33(5):410-423. doi: 10.1089/AID.2016.0204. Epub 2017 Jan 30.

Comparison of Antibody Responses Induced by RV144, VAX003, and VAX004 Vaccination Regimens.

Author information

1
1 Department of Retrovirology, Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok, Thailand .
2
2 Department of Disease Control, Ministry of Public Health , Nonthaburi, Thailand .
3
3 Royal Thai Army , AFRIMS, Bangkok, Thailand .
4
4 Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand .
5
5 Center of Excellence for Biomedical and Public Health Informatics, Faculty of Tropical Medicine, Mahidol University , Bangkok, Thailand .
6
6 Sanofi Pasteur , Swiftwater, Pennsylvania.
7
7 Global Solutions for Infectious Diseases (GSID) , South San Francisco, California.
8
8 U.S. Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, Maryland.
9
9 Henry M. Jackson Foundation for the Advancement of Military Medicine , Bethesda, Maryland.
10
10 The Thai Red Cross AIDS Research Centre , Bangkok, Thailand .
11
11 International Vaccine Institute , Seoul, Republic of Korea.
12
12 Viral Diseases Branch, Walter Reed Army Institute of Research , Silver Spring, Maryland.

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.

KEYWORDS:

HIV vaccines; HSV; IgG; IgG subclasses IgA; RV144; V1 V2; V2; V3; VAX003; VAX004; antibodies; gp120

PMID:
28006952
PMCID:
PMC5439458
DOI:
10.1089/AID.2016.0204
[Indexed for MEDLINE]
Free PMC Article

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