Combining Intramuscular and Intranasal Immunization With the MF59-Adjuvanted Respiratory Syncytial Virus Pre-Fusion Protein Subunit Vaccine Induces Potent Humoral and Cellular Immune Responses in Mice.

Respiratory syncytial virus (RSV) ranks as the second leading cause of infant death globally and a significant contributor to morbidity and mortality among adults over 60 years old. The development of effective RSV vaccines and immunoprophylaxis remains a key focus. In our research, we formulated a protein-based vaccine known as MF59/preF, which combines the RSV pre-fusion (preF) antigen with an MF59-like oil-in-water adjuvant. Intramuscular (IM) or intranasal (IN) immunization of the MF59-adjuvanted preF protein vaccine elicited robust immune responses and neutralizing antibodies against both RSV A2 and RSV B strains, with the IM showing a particularly pronounced effect. Notably, IN immunization with MF59/preF demonstrated superior mucosal immunity, characterized by elevated levels of IgA antibodies and an increased frequency of tissue-resident memory T (T(RM)) cells locally. More importantly, the combined IM and IN delivery of the MF59/preF vaccine synergistically enhanced antigen-specific humoral and cellular immune responses at both systemic and mucosal sites. Our study highlights the crucial impact of the route of administration and adjuvanted-protein subunit vaccines on triggering strong humoral and cellular immunity in mice.