Construction and application of a novel respiratory syncytial virus vaccine based on Bacteroides thetaiotaomicron outer membrane vesicles

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, young children, immunocompromised adults, and elderly individuals with comorbidities. Its high pathogenicity and associated mortality impose a substantial disease burden on public health. Vaccination represents a key strategy for preventing RSV infection. However, currently approved RSV vaccines exhibit limitations. For instance, Abrysvo and Arexvy pose potential safety risks in clinical use, and the long-term protective efficacy of mRESVIA may wane over time. Therefore, this article proposes and explores a novel RSV vaccine strategy utilizing Bacteroides thetaiotaomicron outer membrane vesicles (Bt OMVs) as a delivery platform. This strategy capitalizes on the unique advantages of Bt OMVs, including efficient mucosal delivery, low inherent toxicity, and targeted modulation of T cell homeostasis—specifically enhancing Treg and Th1 responses while suppressing excessive Th2 and Th17 activation, which serves as the core mechanism for preventing vaccine-enhanced disease (VED)—to effectively present the RSV F protein antigen. It offers a novel approach to develop next-generation RSV vaccines that combine durable protection with enhanced clinical safety.