Immunogenicity of TB vaccine H56 in non-human primates (VAC4P.1113)

Abstract

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health problem. Several TB vaccine candidates are currently in various stages of development and clinical testing, including the protein subunit vaccine H56, from Statens Serum Institute (Copenhagen, Denmark). The cationic liposome adjuvant CAF09 was recently developed to enhance the CD4 and CD8 T cell response when administered with H56 vaccine. We vaccinated non-human primates (NHP) with H56 vaccine and CAF09 adjuvant by intranasal and subcutaneous routes and compared differences in immunogenicity. We measured the immune response to the vaccine in blood samples at multiple time points by IFN-γ ELISPOT and intracellular cytokine staining (IFN-γ, IL-2, TNF, IL-17, IL-6, IL-10) and in bronchoalveolar lavage fluid (BAL) by intracellular cytokine staining. NHPs were challenged with Mtb, and recall responses assessed. Frequencies of activated T cells producing cytokines transiently increased following vaccinations, but were generally low. CD4 responses were highest to the Ag85B vaccine component, while CD8 responses were highest to the Rv2660c vaccine component. There were no significant differences in cytokine production between the two vaccination routes in blood or BAL. This may lead to further H56/CAF09 vaccine trials in NHPs with Mtb challenge and future clinical trials, while strengthening understanding of the immune response necessary for protection from TB.