Advanced Functional Materials, 28 August 2025
Abstract
Human respiratory syncytial virus (RSV) is a leading global cause of severe respiratory infections in infants, substantial morbidity in adults, and elevated mortality among elderly individuals. While recently, the Food and Drug Administration (FDA)-approved subunit and mRNA-based RSV vaccines have demonstrated clinical efficacy, next-generation platforms capable of eliciting synergistic humoral and cellular immunity remain critical. Here, a self-assembled nanovaccine platform incorporating either prefusion-stabilized F protein variants (DS-Cav1, DS2) or post-fusion F (PF) conjugated to the PC7A polymer and co-adsorbed with the TLR9 agonist CpG is developed. Comparative immunogenicity analyses in C57BL/6J and BALB/c mice demonstrated that the RSV F protein-PC7A/CpG combinatorial nanovaccine platform outperformed individual adjuvant formulations (CpG-alone or PC7A-alone) in eliciting neutralizing antibody titers against both the RSV A and B subtypes. BALB/c models further revealed comprehensive cellular immune activation, characterized by significant expansion of antigen-specific TNF-α+ CD4+/CD8+ T cells, IL-4+ T helper subsets, and Granzyme B+ cytotoxic T lymphocytes. During the live RSV challenge, the vaccinated groups, especially the DS2-PC7A/CpG nanovaccine cohort, exhibited a significant reduction in pulmonary viral loads and attenuated airway inflammation. These findings highlight the DS2-PC7A/CpG nanovaccine as a potent dual-adjuvanted candidate and immune synergy to advance clinical RSV vaccine development.
Products: RVV02801, RVV02814, RVV02816, Anti-HRSV F/Fusion glycoprotein F0 Antibody (Am14), Anti-HRSV-A F/Fusion glycoprotein F0 Antibody (MPE8), Anti-HRSV-A F/Fusion glycoprotein F0 Antibody (101F)