• Sara Suliman, Angelique Kany Kany Luabeya, Hennie Geldenhuys, Michele Tameris, Soren T Hoff, Zhongkai Shi, Dereck Tait, Ingrid Kromann, Morten Ruhwald, Kathryn Tucker Rutkowski, Barbara Shepherd, David Hokey, Ann M Ginsberg, Willem A Hanekom, Peter Andersen, Thomas J Scriba, Mark Hatherill, and H56-035 Trial Group.
• 1 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and.
• Am. J. Respir. Crit. Care Med. 2019 Jan 15; 199 (2): 220-231.

RationaleGlobal tuberculosis (TB) control requires effective vaccines in TB-endemic countries, where most adults are infected with Mycobacterium tuberculosis (M.tb).ObjectivesWe sought to define optimal dose and schedule of H56:IC31, an experimental TB vaccine comprising Ag85B, ESAT-6, and Rv2660c, for M.tb-infected and M.tb-uninfected adults.MethodsWe 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 of different concentrations of H56 in 500 nmol of IC31 to enable dose selection for further vaccine development. Subsequently, QFT-positive and QFT-negative participants were randomized to receive two or three vaccinations to compare potential schedules. Participants were followed for safety and immunogenicity for 292 days.Measurements And Main ResultsH56:IC31 showed acceptable reactogenicity profiles irrespective of dose, number of vaccinations, or M.tb infection. No vaccine-related severe or serious adverse events were observed. The three H56 concentrations tested induced equivalent frequencies and functional profiles of antigen-specific CD4 T cells. ESAT-6 was only immunogenic in QFT-negative participants who received three vaccinations.ConclusionsTwo or three H56:IC31 vaccinations at the lowest dose induced durable antigen-specific CD4 T-cell responses with acceptable safety and tolerability profiles in M.tb-infected and M.tb-uninfected adults. Additional studies should validate applicability of vaccine doses and regimens to both QFT-positive and QFT-negative individuals. Clinical trial registered with www.clinicaltrials.gov (NCT01865487).

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