Abstract:
Background: We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring
whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could
improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous
HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania.
Methods: Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1 mg intradermally
(id), n = 20, or 3.8 mg intramuscularly (im), n = 20, or placebo, n = 20, using a needle-free injection
device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B
were given at weeks 0, 4 and 12. Recombinant MVA (108 pfu) expressing HIV-1 Env, Gag, Pol of CRF01 AE
or placebo was administered im at month 9 and 21.
Results: The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%)
vaccinees had IFN- ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%)
vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost,
28/29 (97%) vaccinees had IFN- ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed
recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining
for Gag-specific IFN- /IL-2 production showed both CD8+ and CD4+ T cell responses. All vaccinees had
HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and
26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29
vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01 AE pseudoviruses
in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives,
depending upon the clade B or CRF01 AE virus tested.
