Engineering a Dual Vaccine Against COVID-19 and Tuberculosis

The COVID-19 pandemic, caused by SARS-CoV-2 virus, has been one of the top public health threats across the world over the past three years. BCG is currently the only licensed vaccine for tuberculosis, one of the deadliest infectious diseases in the world, that is caused by . In the past decades, recombinant BCG has been studied as a novel vaccine vector for other infectious diseases in humans besides tuberculosis, such as viral infections. In the current study, we generated a recombinant BCG strain AspikeRBD that expresses a fusion protein consisting of Ag85A protein and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using synthetic biology technique. Our results show that the recombinant BCG strain successfully expressed this fusion protein. Interestingly, the recombinant BCG strain AspikeRBD significantly induced SARS-CoV-2 spike-specific T cell activation and IgG production in mice when compared to the parental BCG strain, and was more potent than the recombinant BCG strain expressing SARS-CoV-2 spike RBD alone. As expected, the recombinant BCG strain AspikeRBD activated an increased number of Ag85A-specific IFNγ-releasing T cells and enhanced IgG production in mice when compared to the parental BCG strain or the BCG strain expressing SARS-CoV-2 spike RBD alone. Taken together, our results indicate a potential application of the recombinant BCG strain AspikeRBD as a novel dual vaccine against SARS-CoV-2 and in humans.