1. 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.
- Author
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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, Ackland J, Syvertsen K, Zachariah D, Anas K, Sayeed E, Lombardo A, Gilmour J, Cox J, Fast P, and Priddy F
- Subjects
- AIDS Vaccines administration & dosage, AIDS Vaccines adverse effects, Adenoviridae genetics, Adenoviridae immunology, Adjuvants, Immunologic, Adolescent, Adult, Antibodies, Neutralizing, Antibodies, Viral immunology, Female, Genetic Vectors genetics, Genetic Vectors immunology, HIV Antibodies blood, HIV Antibodies immunology, HIV Infections immunology, HIV-1 genetics, Human Immunodeficiency Virus Proteins genetics, Humans, Immunity, Cellular, Immunity, Humoral, Interferon-gamma biosynthesis, Interferon-gamma blood, Male, Recombinant Fusion Proteins genetics, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Vaccination, Young Adult, AIDS Vaccines immunology, Black People, HIV Infections prevention & control, HIV-1 immunology, Healthy Volunteers, Human Immunodeficiency Virus Proteins immunology, Recombinant Fusion Proteins immunology
- 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-γ 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-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. 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., Trial Registration: ClinicalTrials.gov NCT01264445.
- Published
- 2015
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