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

PLoS One. 2015 May 11;10(5):e0125954. doi: 10.1371/journal.pone.0125954. eCollection 2015.

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / adverse effects
  • AIDS Vaccines / immunology*
  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Adjuvants, Immunologic
  • Adolescent
  • Adult
  • Antibodies, Neutralizing
  • Antibodies, Viral / immunology
  • Blacks*
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • HIV Antibodies / blood
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Healthy Volunteers*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / immunology*
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Male
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vaccination
  • Young Adult

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • HIV Antibodies
  • Human Immunodeficiency Virus Proteins
  • Recombinant Fusion Proteins
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT01264445

Grant support

This work was supported by GSK Biologicals SA and the International AIDS Vaccine Initiative. IAVI’s work is made possible by generous support from many donors including: the Bill & Melinda Gates Foundation; the Ministry of Foreign Affairs of Denmark; Irish Aid; the Ministry of Finance of Japan in partnership with the World Bank; the Ministry of Foreign Affairs of the Netherlands; the Norwegian Agency for Development Cooperation (NORAD); the United Kingdom Department for International Development (DFID), and the United States Agency for International Development (USAID). The full list of IAVI donors is available at www.iavi.org. This study is made possible by the generous support of the American people through USAID. The contents are the responsibility of the International AIDS Vaccine Initiative and do not necessarily reflect the views of USAID or the United States Government.