A Nasal Vaccine Displaying Anthrax Antigen on the Surface of <i>Lactiplantibacillus plantarum</i> Induces Protective Mucosal Immunity against Anthrax Toxin

Anthrax, particularly inhalational anthrax, poses a severe threat due to its high fatality rate and potential misuse as a biological weapon. Current anthrax vaccines require multiple injections, which limits their practicality and underscores the need for improved, user-friendly vaccination strategies. In this study, we developed a novel nasal booster vaccine platform aimed at preventing inhalational anthrax by inducing mucosal immunity at the pathogen's entry site, the respiratory tract. We successfully engineered a biologically safe <i>Lactiplantibacillus plantarum</i> (<i>L. plantarum</i>) strain to display the anthrax protective antigen (PA) on its surface. Following systemic priming by intramuscular immunization, nasal boosting with this recombinant <i>L. plantarum</i> strain significantly enhanced protective antigen (PA)-specific mucosal IgA production in both nasal and bronchoalveolar lavage fluids. Importantly, mucosal IgA antibodies elicited through this nasal boosting strategy effectively neutralized anthrax lethal toxin. Our findings indicate that recombinant <i>L. plantarum</i> expressing PA represents a promising nasal vaccine booster platform, potentially replacing traditional intramuscular boosters, and paving the way for the development of effective and easily administered mucosal vaccines against anthrax and other respiratory pathogens.