P26.08
Background: We evaluated the effects of two adjuvanted clade C Env protein immunizations after multi-clade HIV-DNA and HIV-MVA priming in healthy Tanzanian volunteers. The DNA included a plasmid encoding Clade C Env.
Methods: Thirty-five volunteers primed three times with HIV-DNA encoding HIV-1 subtypes A, B, and C and boosted twice with MVA CMDR expressing CRF01_AE were further boosted with two doses of trimeric CN54rgp140 subtype C adjuvanted with GLA-AF (IDRI; rgp140/ GLA). Five placebo recipients received the same immunizations with rgp140/GLA. Antibody (Ab)- and cell-mediated immune responses were assessed.
Results: Boosting DNA/MVA vaccine recipients (n=35) twice with rgp140/GLA increased median anti-CN54gp140 IgG titers considerably from 900 to 24300 (p<0.0001). After rgp140/GLA boosts DNA/MVA vaccines had higher median rgp140 IgG titers (24300) compared to placebo recipients (2700, p=0.0316) and those with elevated titers of ≥900 after the DNA/MVA prime had higher titers after the first (p=0.0009) and second rgp140/GLA boost (p=0.0449). No significant increase in neutralizing antibody activity was seen in an infectious molecular clone (IMC)/PBMC assay against GS015 subtype C or CM235 CRF01_AE after the second rgp140/GLA. Only one vaccinee developed antibody-dependent cellular cytotoxicity-Ab to HIV 1086 subtype C IMC after two rgp140/GLA vaccinations. The IFN-g ELISpot response rate to Env increased from 29.4% (10/34) at the time of the first rgp140/GLA to 68.6% (24/35) after the second.
Conclusions: DNA/MVA priming had a significant effect on anti-CN54gp140 IgG responses after boosting with rgp140/GLA. Immunization with rgp140/GLA enhanced binding Ab responses and cell-mediated immune responses in HIV-DNA/MVA-primed Tanzanian vaccines, but no significant increase in functional humoral responses could be detected.
