Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection
Respiratory syncytial virus(RSV) is a major cause of severe lower respiratory tract disease in infancy and early childhood. Despite its importance as a pathogen, there is no licensed vaccine against RSV. The G glycoprotein of RSV, a major attachment protein, is a potentially important target for protective antiviral immune responses. Here, a recombinant replication-deficient adenovirus-based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein(amino acids 130 to 230) engineered by codon optimization and tandem repetition for higher level expression, was constructed and evaluated for its potential as an RSV vaccine in murine model. A single intranasal immunization with rAd/3xG provided potent protection against RSV challenge which lasted for more than 10 weeks. Strong mucosal IgA responses were also induced by single intranasal immunization but not by intramuscular or oral administration of rAd/3xG. Interestingly, neither IFN-γ nor IL-4-producing CD4 T cells directed to I-E^(d)-restricted epitope were detected in the lungs of rAd/3xG-immune mice upon challenge, whereas vvG priming elicited strong Th1/Th2-mixed CD4 T-cell responses. Lung eosinophilia and vaccine-induced weight loss were significantly lower in rAd/3xG-immune group than vvG-primed group. Together, our data demonstrate that a single intranasal administration of rAd/3xG elicits beneficial protective immunity and represents a promising vaccine regimen against RSV infection.