Details

Autor(en) / Beteiligte

• Omosa-Manyonyi, Gloria
• Mpendo, Juliet
• Ruzagira, Eugene
• Kilembe, William
• Chomba, Elwyn
• Roman, François
• 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
• Doherty, T. Mark

Titel

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

Ist Teil von

• PloS one, 2015-05, Vol.10 (5), p.e0125954-e0125954

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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. ClinicalTrials.gov NCT01264445.