Single mucosal immunization of recombinant adenovirus-based vaccine expressing F1 protein fragment induces protective mucosal 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 fusion (F) protein of RSV is a potentially important target for protective antiviral immune responses. Here, we studied the immune responses elicited by recombinant replication-deficient adenovirus (rAd)-based vaccines expressing the soluble F1 fragment of F protein (amino acids 155-524) in murine model. The expression of secreted F1 fragment by rAd was significantly increased by codon optimization. Strong mucosal IgA response was induced by single intranasal immunization of codon-optimized vaccine, rAd/F1co, but not by rAd/F1wt. A single intranasal immunization with rAd/F1co provided potent protection against subsequent RSV challenge. Interestingly, neither serum Ig nor T-cell response directed to F protein was detected in the rAd/F1co-immune mice, suggesting that protective immunity by rAd/F1co is mainly mediated through mucosal IgA induction. Indeed, co-delivery of cholera toxin B subunit significantly enhanced mucosal IgA responses by the optimized vaccine, which correlates with protective efficacy. Taken together, our data demonstrate that a single intranasal administration of rAd/F1co is sufficient for the protection and represents a promising prophylactic vaccination regimen against RSV infection.
Kim
Sol
S
Division of Life & Pharmaceutical Sciences, and the Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul 120-750, Republic of Korea.
Jang
Ji-Eun
JE
Yu
Jae-Rang
JR
Chang
Jun
J
D000256:Adenoviridae / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D017778:Vaccines, Combined / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D022261:Respiratory Syncytial Virus Vaccines; D017778:Vaccines, Combined; D014760:Viral Fusion Proteins