A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults
05/2015
Journal Article
Authors:
Omosa-Manyonyi, G.;
Mpendo, J.;
Ruzagira, E.;
Kilembe, W.;
Chomba, E.;
Roman, F.;
Bourguignon, P.;
Koutsoukos, M.;
Collard, A.;
Voss, G.;
Laufer, D.;
Stevens, G.;
Hayes, P.;
Clark, L.;
Cormier, E.;
Dally, L.;
Barin, B.;
, ;
Gilmour, J.;
Cox, J.;
Fast, P.;
Priddy, F.
Secondary:
PLoS One
Volume:
10
Pagination:
e0125954
URL:
http://www.ncbi.nlm.nih.gov/pubmed/25961283
Abstract:
BACKGROUND: Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. METHODS: In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. RESULTS: The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-gamma ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-alpha, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-gamma +/- IL2 or TNF-alpha. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. CONCLUSION: Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses.
