In situ self-growth nano-selenium-loaded peptidoglycan-based biomimetic bioparticles as a versatile immunoregulatory delivery platform for subunit vaccines.

Vaccination is the most effective and cost-efficient strategy for preventing infectious diseases. Bacterial-like particles (BLP), which retain peptidoglycan from bacterial cell walls after heat-acid treatment, offer a promising platform for enhancing the immunogenicity of subunit vaccines. However, BLP-based carriers typically require multiple doses or adjuvants to achieve the desired immune response. Despite various strategies to optimize BLP, challenges remain, including redox imbalances induced by vaccination or pathogens, impairing immune responses, and the insufficient exploration of methods to shorten the immune priming window, limiting rapid protection. In this study, we developed an in situ self-grown nano‑selenium-loaded bacterium-like particle (SeBLP), utilizing a microbial biomimetic strategy that integrates self-growth deposition and subsequent acidic stabilization treatment. This approach directly constructs speckled selenium nanoparticles onto a probiotic scaffold, enhancing fabrication efficiency, cost-effectiveness, and biocompatibility. Compared to traditional BLP, SeBLP demonstrates stable antigen loading capacity, superior antioxidant properties, and significantly alleviates vaccination-related side effects. Moreover, SeBLP significantly enhances vaccine efficacy against model antigens, generating a balanced immune response. Additionally, SeBLP, as a carrier, provides rapid and complete protection to mice against lethal infections, balancing inflammation, regulating oxidative stress, and enabling quick recovery. Our study demonstrates that SeBLP, an innovative immunoregulatory delivery platform, employs a microbial biomimetic approach to modulate redox balance, enhancing immune response quality and reducing the priming window for rapid protection. These findings underscore the potential of optimizing biomaterial-based vaccine carriers, offering insights into improving subunit vaccine efficacy and the integration of selenium nanoparticles in advanced vaccine formulations.