Single Intranasal Immunization with Recombinant Adenovirus-Based Vaccine Induces Protective Immunity against Respiratory Syncytial Virus Infection (B192)

Abstract

Abstract 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/3×G, expressing the soluble core domain of G glycoprotein spanning amino acids 130 to 230, was engineered by codon optimization and tandem repetition for higher level expression, and evaluated for its potential to be used as an RSV vaccine in murine model. A single intranasal but not intramuscular immunization with rAd/3xG provided potent protection against RSV challenge at an improved level over inoculation of a recombinant vaccinia virus expressing whole G protein (vvG). Strong mucosal secretory IgA responses were induced by single intranasal immunization but not by intramuscular administration or immunization of vvG, while comparable serum IgG responses were observed in each group. Interestingly, rAd/3xG immunization did not induce detectable CD4 T-cell response whereas vvG priming strongly elicited CD4 T-cell response against I-Edrestricted G epitope (amino acids 183 to 195). RSV-induced weight loss was significantly lower in rAd/3xG-immunized group than vvG-immunized group. Thus, our data demonstrate that a single intranasal administration of rAd/3xG elicits beneficial protective immunity and represents a novel vaccine regimen capable of providing mucosal protection against RSV infection.