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

Biberfeld, Gunnel1; Aboud, S2; Bakari, M2; Nilsson, C1; Moshiro, C2; Aris, E3; Lyamuya, E2; Janabi, M3; Godoy-Ramirez, K1; Earl, P4; Robb, M5; Marovich, M5; Michael, N5; Wahren, B1; Pallangyo, K2; Mhalu, F2; Sandström, E6for the HIVIS study group

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 59
doi: 10.1097/01.qai.0000397331.49493.a3

1Karolinska Institutet and the Swedish Institute for Infectious Disease Control, Solna, Sweden; 2Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 3Muhimbili National Hospital, Dar es Salaam, Tanzania; 4National Institute of Allergy and Infectious Diseases/National Institute of Health, Bethesda, Maryland, USA; 5Walter Reed Army Institute for Research, Rockville, Maryland, USA; and 6Karolinska Institutet, Södersjukhuset, Stockholm, Sweden

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.

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