Vectored Immunoprophylaxis for Mucosal Immunity: Advances and Challenges Associated with Recombinant Secretory IgA Expression.

Existing vectored immunoprophylaxis (VIP) approaches have primarily focused on IgG, which provides systemic protection but is less specialized in mucosal immunity. In contrast, secretory IgA (sIgA) plays a central role at epithelial surfaces, promoting pathogen neutralization while limiting inflammation. Although monoclonal IgA therapies are effective, their short half-life requires repeated dosing. Thus, VIP strategies enabling sustained sIgA expression at mucosal sites could transform mucosal infection prevention and treatment. This review outlines the key challenges associated with in vivo IgA expression and discusses critical considerations for VIP-mediated IgA delivery at mucosal surfaces, with emphasis on its potential for clinical translation. We provide a detailed overview of platforms for targeted IgA expression, including adeno-associated virus (AAV), adenoviral and lentiviral vectors, and lipid nanoparticle-based systems, alongside relevant routes of administration. Additionally, we examine emerging strategies to enhance the robustness, durability, and localization of IgA expression in vivo. Overall, VIP-enabled IgA expression represents an emerging strategy for enhancing mucosal immunity, with continued advances required to establish its role in the prevention and treatment of mucosal infections.