Advertisement

 

 

DNA priming increases frequency of T-cell responses to a VSV HIV vaccine with specific enhancement of CD8(+) T-cell responses by IL-12 pDNA.

DNA priming increases frequency of T-cell responses to a VSV HIV vaccine with specific enhancement of CD8(+) T-cell responses by IL-12 pDNA.
Author Information (click to view)

Li SS, Kochar NK, Elizaga M, Hay CM, Wilson GJ, Cohen KW, De Rosa SC, Xu R, Ota-Setlik A, Morris D, Finak G, Allen M, Tieu HV, Frank I, Sobieszczyk ME, Hannaman D, Gottardo R, Gilbert PB, Tomaras GD, Corey L, Clarke DK, Egan MA, Eldridge JH, McElrath MJ, Frahm N, ,


Li SS, Kochar NK, Elizaga M, Hay CM, Wilson GJ, Cohen KW, De Rosa SC, Xu R, Ota-Setlik A, Morris D, Finak G, Allen M, Tieu HV, Frank I, Sobieszczyk ME, Hannaman D, Gottardo R, Gilbert PB, Tomaras GD, Corey L, Clarke DK, Egan MA, Eldridge JH, McElrath MJ, Frahm N, , (click to view)

Li SS, Kochar NK, Elizaga M, Hay CM, Wilson GJ, Cohen KW, De Rosa SC, Xu R, Ota-Setlik A, Morris D, Finak G, Allen M, Tieu HV, Frank I, Sobieszczyk ME, Hannaman D, Gottardo R, Gilbert PB, Tomaras GD, Corey L, Clarke DK, Egan MA, Eldridge JH, McElrath MJ, Frahm N, ,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Clinical and vaccine immunology : CVI 2017 09 20() pii 10.1128/CVI.00263-17

Abstract

HVTN 087 assessed the effect of increasing doses of pIL-12 adjuvant on the immunogenicity of a HIV-1 multi-antigen (MAG) DNA vaccine delivered by electroporation and boosted with an attenuated VSV-Gag vaccine. We randomized 100 healthy adults to receive placebo, or 3mg HIV-MAG (gag/pol, env, nef/tat/vif) DNA vaccine co-administered with pIL-12 at 0μg, 250μg, 1,000μg or 1,500μg intramuscularly by electroporation at 0, 1 and 3 months followed by intramuscular inoculation with 3.4×10(7) PFU VSV-Gag vaccine at 6 months. Immune responses were assessed after prime, boost and 6 months after the last vaccination. High dose pIL-12 increased the magnitude of CD8(+) T cell responses post boost compared to no pIL-12 (P=0.02), while CD4(+) T-cell responses after the prime were higher in the absence of pIL-12 compared to low and medium dose pIL-12 (P≤0.05). The VSV boost increased Gag-specific CD4(+) and CD8(+) T-cell responses in all groups (P<0.001 for CD4(+) T cells), inducing a median of four Gag epitopes in responders. Six to nine months after the boost, responses decreased in magnitude, but CD8(+) T-cell response rates were maintained. The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in HVTN 090, leading to broad epitope targeting and maintained CD8(+) T-cell response rates at early memory. The addition of a high dose pIL-12 given with a DNA prime by electroporation and boosted with VSV-Gag increased CD8(+) but decreased CD4(+) T-cell responses. This approach may be advantageous in reshaping the T-cell responses to a variety of chronic infections or tumors.

Submit a Comment

Your email address will not be published. Required fields are marked *

three × five =

[ HIDE/SHOW ]