Biopolymer-Antigen Conjugate Vaccines for Prevention of Tularemia

Abstract Francisella tularensis, the causative agent of tularemia, is a facultative intracellular pathogen categorized as a tier I bioterrorism agent. The current live vaccine strain (LVS) vaccine poses safety and virulence concerns, advocating the need for a safer alternative. In this study, we demonstrated a combination of antigens FopA, Tul4, SucB, and DnaK conjugated to biopolymer particles (BPs) as a multivalent subunit vaccine that not only induces LVS and SchuS4-specific antibody titers but also confers protective immunity with differential cytokine profiles upon LVS challenge. This multivalent vaccine conferred 80% survival in mice, with antibodies of opsonizing ability and rapid recovery from weight loss. The production of these biopolymer conjugate vaccines was achieved in one step inside engineered Escherichia coli and is not only cost-effective but also leads to thermostable formulations, eliminating the need for cold-chain transport and storage. E. coli fermentation-based production avoids the need for high-containment facilities. Collectively, the FopA-BP-Tul4, SucB-BP, and Dnak-BP combined formulations hold the promise for the development of a robust subunit vaccine for the prevention of tularemia.