Vaccine 2017 02 1735(12) 1652-1661 pii 10.1016/j.vaccine.2017.01.055
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.
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 CD4(+) T cell responses.
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 CD4(+) T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4(+) T cell expansion, IFN-γ production and multifunctional CD4(+) Th1 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.
The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4(+) T 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.
ClinicalTrials.gov, NCT02066428 and NCT02074956.