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

Karnasuta et al., AIDS Res Hum Retroviruses (2016) - PMID: 28006952

Product(s) used in this publication:  Specialty Peptides

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 CycV2 and CycV3 peptides and gp70V1V2 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 gp70V1V2 but VAX004 responses to 92TH023 gp70V1V2 were weak. All CycV2 responses were undetectable in VAX004 while 92TH023 gp70V1V2 were detected in both RV144 and VAX003 but MN CycV2 were detected only in VAX003. Multiple protein vaccinations in VAX trials did not improve magnitude or durability of V1V2 and CycV2 antibodies. HSV 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.

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