The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity and protection following immunization with an adenoviral-based RSV vaccine encoding for the fusion protein F (Ad5.RSV-F) and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (IN) and/or intramuscularly (IM) and subsequently challenged with RSV/A/Tracy (IN) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given IM or IN, which correlated with reduced replication of virus in noses and lungs after challenge. Neutralizing antibody responses followin... More
The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity and protection following immunization with an adenoviral-based RSV vaccine encoding for the fusion protein F (Ad5.RSV-F) and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (IN) and/or intramuscularly (IM) and subsequently challenged with RSV/A/Tracy (IN) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given IM or IN, which correlated with reduced replication of virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5.RSV-F at 1??1011 viral particles (v.p.) elicited antibody titers 64- to 256- fold greater than those seen after natural infection. CRs boosted with Ad5.RSV-F IN 28 days after an IM dose also had significant increases in neutralizing antibody titers. Antibody affinity for different F protein antigenic sites revealed substantial differences between antibodies elicited by Ad5.RSV-F as compared with those seen after RSV infection; differences in antibody profiles were also seen in CRs given Ad5.RSV-F IM vs. IN. Ad5.RSV-F priming did not result in enhanced disease following live virus challenge in contrast with histopathology seen in CRs given formalin-inactivated-RSV/A/Burnett vaccine.
