Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations. A Double-Blind, Placebo-controlled, Dose-Selection Trial

• DOI: 10.1164/rccm.201802-0366oc
• Publication Date: 2018-08-09T21:30:30Z
• Authors: Sara Suliman; Angelique Kany Ka...; Hennie Geldenhuys; Michele Tameris; Soren T. Hoff; Zhongkai Shi; Dereck Tait; Ingrid Kromann; Morten Ruhwald; Kathryn Tucker Ru...; Barbara Shepherd; David Hokey; Ann M. Ginsberg; Willem A. Hanekom; Peter Andersen; Thomas J. Scriba; Mark Hatherill; Rachel Elizabeth ...; Lynnett Stone; Anne Marie Swarts; Raida Onrust; Gail Jacobs; Lorraine Coetzee; Gloria Khomba; Bongani Diamond; Alessandro Companie; Ashley Veldsman; Humphrey Mulenga; Yolundi Cloete; Marcia Steyn; Hadn Africa; Lungisa Nkantsu; Erica Smit; Janelle Botes; Nicole Bilek; Simbarashe Mabwe
• Keywords: Reactogenicity; Tuberculosis vaccines; QuantiFERON; Tolerability

Global tuberculosis (TB) control requires effective vaccines in TB-endemic countries, where most adults are infected with Mycobacterium (M.tb).We sought to define optimal dose and schedule of H56:IC31, an experimental TB vaccine comprising Ag85B, ESAT-6, Rv2660c, for M.tb-infected M.tb-uninfected adults.We enrolled 98 healthy, HIV-uninfected, bacillus Calmette-Guérin-vaccinated, South African adults. M.tb infection was defined by QuantiFERON-TB (QFT) assay. QFT-negative participants received two vaccinations different concentrations H56 500 nmol IC31 enable selection further development. Subsequently, QFT-positive were randomized receive or three compare potential schedules. Participants followed safety immunogenicity 292 days.H56:IC31 showed acceptable reactogenicity profiles irrespective dose, number vaccinations, infection. No vaccine-related severe serious adverse events observed. The tested induced equivalent frequencies functional antigen-specific CD4 T cells. ESAT-6 only immunogenic who vaccinations.Two H56:IC31 at the lowest durable T-cell responses tolerability Additional studies should validate applicability doses regimens both individuals. Clinical trial registered www.clinicaltrials.gov (NCT01865487).