Article Publish Status: FREE
Abstract Title:

Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials.

Abstract Source:

Vaccine. 2017 03 14 ;35(12):1652-1661. Epub 2017 Feb 17. PMID: 28216183

Abstract Author(s):

Maria Norrby, Timo Vesikari, Lars Lindqvist, Markus Maeurer, Raija Ahmed, Shahnaz Mahdavifar, Sean Bennett, J Bruce McClain, Barbara M Shepherd, Daner Li, David A Hokey, Ingrid Kromann, Søren T Hoff, Peter Andersen, Adriëtte W de Visser, Simone A Joosten, Tom H M Ottenhoff, Jan Andersson, Susanna Brighenti

Article Affiliation:

Maria Norrby


BACKGROUND: Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant.

METHODS: BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4T cell responses.

RESULTS: H4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4T cell expansion, IFN-γ production and multifunctional CD4Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose.

CONCLUSIONS: The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02066428 and NCT02074956.

Study Type : Human Study

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Sayer Ji
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