VALIDATE Seminar - Spore-FP1 mucosal vaccine candidate for TB
About the Seminar: Two talks followed by a Q&A
From mice to NHP: testing the Spore-FP1 mucosal vaccine candidate in animal models
Prof Rajko Reljic, St George's University of London, UK
TB remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on the surface of inactivated Bacillus subtilis spores. It conferred significant protection in mice and guinea pigs when used as a mucosal boost to BCG. In NHP, aerosolised Spore-FP1 induced higher antigen specific immune responses, including IFN-g secreting CD4 T-cells and Th17 cells, as well as specific IgA and IgG in nasal swab washings and sera, but did not improve upon the efficacy afforded by BCG alone, either in terms of disease pathology or lung bacterial burden. This highlights the challenges in reconciling disparate outcomes from different animal models of MTB infection.
Immunogenicity of Spore-FP1 and Nano-FP1 as a post-exposure TB vaccine candidate
Mr Emil Vergara, St George's University of London, UK
Post-exposure vaccination is an attractive therapeutic strategy for TB patients with the aim of working side-by-side with antibiotic therapy to either reduce the duration of treatment, improve cure rates, and lower the risk of relapse. Skewing pre-existing mucosal and systemic immunity towards a more protective phenotype is vital for the success of a post-exposure vaccine. In this study, two subunit vaccine candidates, Spore-FP1 and Nano-FP1, were delivered as a single intranasal dose to mice with pre-existing lung mycobacterial immunity elicited with Mycobacterium bovis BCG. Analysis of lung mucosal T cell responses showed an increasing trend in the frequency of tissue resident memory T cells, antigen specific effector CD4 and CD8 T cells with a Th1 cytokine (IFNγ and TNFα) signature, and mucosal and systemic antibody responses among mice that received candidate vaccines. These results support further testing of Spore-FP1 and Nano-FP1 as post-exposure TB vaccines.
About the Speakers
Prof Rajko Reljic's TB work involves the use of several mucosal vaccine delivery systems, including nanoparticles, inactivated bacterial spores, liposomes and self-adjuvanting recombinant immune complexes. He is the scientific lead and the Coordinator of the EMI-TB consortium, a European Union-funded mucosal TB vaccine initiative that involves 14 research groups from Europe and Africa.
Emil Vergara is a PhD candidate at St. George's University of London, where he is conducting research on post-exposure immunization strategies against multi-drug resistant tuberculosis (MDR-TB). His work focuses on both passive and active immunization methods. Emil's research also involves using ex vivo mycobacterial growth inhibition assay (MGIA) to evaluate vaccine- or infection-induced immunity.
