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 a murine model. A single intranasal immunization with rAd/3xG provided potent protection against RSV challenge which lasted for more than 10 weeks. Strong mucosal immunoglobulin A responses were also induced by a single intranasal immunization but not by intramuscular or oral administration of rAd/3xG. Interestingly, neither gamma interferon- nor interleukin-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 priming with vaccinia virus expressing RSV G (vvG) elicited strong Th1/Th2 mixed CD4 T-cell responses. Lung eosinophilia and vaccine-induced weight loss were significantly lower in the rAd/3xG-immune group than in the 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.
Yu
Jae-Rang
JR
College of Pharmacy, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-Mun Gu, Seoul 120-750, Korea.
Kim
Sol
S
Lee
Jee-Boong
JB
Chang
Jun
J
D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000302:isolation & purification
D000914:Antibodies, Viral