146 Strong and Broad Immunogenicity of a Multigene, Multiclade HIV-1 DNA Prime MVA Boost Vaccine Regimen Among Healthy Tanzanian Volunteers

A phase I trial (HIVIS01/02) of a multigene, multiclade HIV-1 DNA prime heterologous MVA boost vaccine regimen among healthy volunteers in Sweden showed that the vaccines were safe and highly immunogenic (J Inf Dis 2008;198:1482-90). A phase I/II trial (HIVIS03) using the same vaccine constructs has subsequently been conducted in Dar es Salaam, Tanzania. Sixty HIV-uninfected volunteers randomised to three groups of 20 received HIV-DNA vaccine at 1 mg intradermally (i.d) or 3.8 mg intramuscularly (i.m.) or placebo using a needle-free device. The DNA plasmids containing HIV-1 gp160 subtypes A,B,C, revB, gag A,B and RtmutB were given at months 0, 1 and 3. The volunteers were boosted i.m. with 108 pfu of MVA containing HIV-1 env, gag, pol of CRF01A_E or placebo at months 9 and 21.Two to four weeks after the second HIV-MVA boost, 28 (97%) of 29 vaccinees had positive IFN-gamma ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env peptides. The i.d. primed vaccinees showed higher immune responses to Env compared to the i.m. primed vaccinees. Intracellular cytokine staining for Gag-specific IFN-gamma/IL-2 production 4 weeks after the second HIV-MVA boost showed both CD8 and CD4 T-cell responses. All of 25 vaccinees had lymphoproliferative responses of a similar high magnitude to AT-2-treated HIV antigens from 3 different subtypes (donated by J Lifson, NCI, USA). After the second HIV-MVA boost, 26/29 (90 %) of the vaccinees developed binding antibodies to gp160. In conclusion, this HIV-DNA prime MVA boost vaccine regimen induced strong and broad immune responses in Tanzanian volunteers.