Development of an Adenovirus-Based Respiratory Syncytial Virus Vaccine: Preclinical Evaluation of Efficacy, Immunogenicity, and Enhanced Disease in a Cotton Rat Model

作者：Kim Eun; Okada Kaori; Beeler Judy A; Crim Roberta L; Piedra Pedro A; Gilbert Brian E; Gambotto Andrea^*

来源：Journal of Virology, 2014, 88(9): 5100-5108.

DOI：10.1128/JVI.03194-13

The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity of an adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5. RSV-F) and the protection provided following immunization with Ad5. RSV-F and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) and subsequently challenged with RSV/A/Tracy (i.n.) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5. RSV-F given i.m. or i.n., and these responses correlated with reduced replication of the virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5. RSV-F at 1 x 10(11) viral particles (v.p.) elicited antibody titers 64-to 256-fold greater than those seen after natural infection. CRs boosted with Ad5. RSV-F i.n. 28 days after an i.m. 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 and those seen after RSV infection; differences in antibody profiles were also seen between CRs given Ad5. RSV-F i.m. and CRs given Ad5. RSV-F i.n. Ad5. RSV-F priming did not result in enhanced disease following live-virus challenge, in contrast to the histopathology seen in CRs given the formalin-inactivated RSV/A/Burnett vaccine.

• 出版日期2014-5