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

作者：Omosa Manyonyi Gloria; Mpendo Juliet; Ruzagira Eugene; Kilembe William; Chomba Elwyn; Roman Francois; Bourguignon Patricia; Koutsoukos Marguerite; Collard Alix; Voss Gerald; Laufer Dagna; Stevens Gwynn; Hayes Peter; Clark Lorna; Cormier Emmanuel; Dally Len; Barin Burc; Ackland Jim; Syvertsen Kristen; Zachariah Devika; Anas Kamaal; Sayeed Eddy; Lombardo Angela; Gilmour Jill; Cox Josephine; Fast Patricia; Priddy Frances

来源：PLos One, 2015, 10(5): UNSP e0125954.

DOI：10.1371/journal.pone.0125954

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/AS01(E) or F4/AS01(B) followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01(B); or three co-administrations of Ad35-GRIN and F4/AS01(B). 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.

• 出版日期2015-5-11