AUTHOR=Guthrie Carlyn Monèt , Tan Xuejuan , Meeker Amber Cherry , Self Ashton Elisabeth , Liu Lin , Cheng Yong 

TITLE=Engineering a dual vaccine against COVID-19 and tuberculosis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1273019

DOI=10.3389/fcimb.2023.1273019

ISSN=2235-2988

ABSTRACT=<p>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. <italic>Mycobacterium bovis</italic> BCG is currently the only licensed vaccine for tuberculosis, one of the deadliest infectious diseases in the world, that is caused by <italic>Mycobacterium tuberculosis</italic>. In the past decades, recombinant <italic>M.bovis</italic> 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 <italic>M. bovis</italic> BCG strain AspikeRBD that expresses a fusion protein consisting of <italic>M. tb</italic> 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 <italic>M. bovis</italic> BCG strain successfully expressed this fusion protein. Interestingly, the recombinant <italic>M. bovis</italic> BCG strain AspikeRBD significantly induced SARS-CoV-2 spike-specific T cell activation and IgG production in mice when compared to the parental <italic>M.bovis</italic> BCG strain, and was more potent than the recombinant <italic>M.bovis</italic> BCG strain expressing SARS-CoV-2 spike RBD alone. As expected, the recombinant <italic>M. bovis</italic> BCG strain AspikeRBD activated an increased number of <italic>M. tb</italic> Ag85A-specific IFNγ-releasing T cells and enhanced IgG production in mice when compared to the parental <italic>M.bovis</italic> BCG strain or the BCG strain expressing SARS-CoV-2 spike RBD alone. Taken together, our results indicate a potential application of the recombinant <italic>M. bovis</italic> BCG strain AspikeRBD as a novel dual vaccine against SARS-CoV-2 and <italic>M. tb</italic> in humans.</p>