Broad and potent immune responses to a low dose intradermal HIV-1 DNA boosted with HIV-1 recombinant MVA among healthy adults in Tanzania.

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. Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1mg intradermally (id), n=20, or 3.8mg 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 (10(8)pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ 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-γ 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-γ/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. This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses.

Bakari M ，Aboud S ，Nilsson C ，Francis J ，Buma D ，Moshiro C ，Aris EA ，Lyamuya EF ，Janabi M ，Godoy-Ramirez K ，Joachim A ，Polonis VR ，Bråve A ，Earl P ，Robb M ，Marovich M ，Wahren B ，Pallangyo K ，Biberfeld G ，Mhalu F ，Sandström E ... -  《-》

HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

Nilsson C ，Hejdeman B ，Godoy-Ramirez K ，Tecleab T ，Scarlatti G ，Bråve A ，Earl PL ，Stout RR ，Robb ML ，Shattock RJ ，Biberfeld G ，Sandström E ，Wahren B ... -  《PLoS One》

Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial.

Viegas EO ，Tembe N ，Nilsson C ，Meggi B ，Maueia C ，Augusto O ，Stout R ，Scarlatti G ，Ferrari G ，Earl PL ，Wahren B ，Andersson S ，Robb ML ，Osman N ，Biberfeld G ，Jani I ，Sandström E ... -  《-》

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design.

Viegas EO ，Kroidl A ，Munseri PJ ，Missanga M ，Nilsson C ，Tembe N ，Bauer A ，Joachim A ，Joseph S ，Mann P ，Geldmacher C ，Fleck S ，Stöhr W ，Scarlatti G ，Aboud S ，Bakari M ，Maboko L ，Hoelscher M ，Wahren B ，Robb ML ，Weber J ，McCormack S ，Biberfeld G ，Jani IV ，Sandström E ，Lyamuya E ，TaMoVac study group ... -  《PLoS One》

Broad and potent cellular and humoral immune responses after a second late HIV-modified vaccinia virus ankara vaccination in HIV-DNA-primed and HIV-modified vaccinia virus Ankara-boosted Swedish vaccinees.

Nilsson C ，Godoy-Ramirez K ，Hejdeman B ，Bråve A ，Gudmundsdotter L ，Hallengärd D ，Currier JR ，Wieczorek L ，Hasselrot K ，Earl PL ，Polonis VR ，Marovich MA ，Robb ML ，Sandström E ，Wahren B ，Biberfeld G ... -  《-》