Exploring the oral route of vaccine delivery using recombinant secretory IgA as a vehicle to boost immune responses against tuberculosis in BCG-primed mice

An improved vaccine against tuberculosis (TB) is urgently needed to enhance the impact of TB immunisation offered by BCG, the only licensed TB vaccine, which is currently unable to substantially reduce the number of TB cases globally. Most new TB vaccine candidates use the parenteral and invasive route of immunisation without showing significant superiority to BCG. Wide-ranging vaccination strategies should be considered to improve the chances of finding an ideal TB vaccine. Here, we explore the potential of treating TB with a non-invasive immunisation route, specifically looking at the oral route of vaccination as a potential strategy for developing a new TB vaccine, which is arguably the most preferred route of vaccination due to its ease of administration at a lower cost compared to injectable vaccines. The downstream hostile gut environment poses a major challenge to oral vaccine development. Several strategies for overcoming this challenge have been studied, such as using live-attenuated vectors and nanoparticles. Our group is at an early stage of developing an oral TB vaccine candidate based on a chimeric secretory IgA-Ag85B subunit vaccine constructed to withstand the gut environment and reach the mucosal immune cells to initiate immune responses. We are currently evaluating the immunogenicity of the vaccine candidate as a booster to BCG in a mouse model to further assess its potential. BALB/c mice primed with BCG were given the vaccine candidate orally, with subsequent collection of samples from the euthanised mice 4 weeks post-booster to determine the T-cell responses in the spleen using flow cytometry and the anti-Ag85B IgG levels in serum and the anti-Ag85B IgA levels in bronchoalveolar lavage using ELISA. The findings from this study can offer new knowledge regarding oral immunisation using a recombinant secretory IgA construct that could potentially become a candidate vaccine for future TB vaccine development.