Developing Novel Vaccines against Respiratory Syncytial Virus Infection

Jun Chang

Graduate School of Pharmaceutical Sciences, Ewha Womans University, 11-1 Dae-Hyun Dong, Seo-Dae-MunGu, Seoul 120-750, Korea.

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 is a potentially important target for protective antiviral immune responses. Here, recombinant replication-deficient adenovirus-based vaccine, rAd/3xG, expressing the soluble core domain of G glycoprotein (amino acids 131 to 230), engineered by codon optimization and tandem repetition for higher level expression, was constructed, and evaluated for its potential as prophylactic RSV vaccine in murine model. Strong serum IgG as well as mucosal IgA responses areinduced by intranasal immunization of rAd/3xG. A single intranasal immunization of rAd/3xG vaccines provides potent protection against RSV challenge without vaccine-enhanced immunopathology. We also tested the efficacy of our vaccines against RSV field isolates from Korean pediatric patients and the data show that our vaccine confers protection against challenge of RSV field isolates. We also show that sublingual or intranasal immunization of a bacterially expressed G protein fragment of the same region, designated Gcf, induces strong serum IgG and mucosal IgA responses. Interestingly, these antibody responses could be elicited by Gcf even in the absence of any adjuvant, indicating a novel self-adjuvanting property of our vaccine candidate. Mucosal immunization with Gcf also provides protection against RSV challenge without any significant lung eosinophilia or vaccine-induced weight loss. Together, our data demonstrate that mucosal administration of our vaccine candidates elicit beneficial protective immunity and represent promising vaccine regimens preventing RSV infection.