A viral-vectored RSV vaccine induces long-lived humoral immunity in cotton rats

• Published in: Vaccine Vol. 36; no. 26; pp. 3842 - 3852
• Main Authors: Grieves, Jessica L., Yin, Zhiwei, Garcia-Sastre, Adolfo, Mena, Ignacio, Peeples, Mark E., Risman, Heidi P., Federman, Hannah, Sandoval, Marvin J., Durbin, Russell K., Durbin, Joan E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 18.06.2018; Elsevier Limited
• Subjects: Adaptive immunity; Allergy and Immunology; Animals; antibody formation; Antiviral agents; Asthma; B cell memory; childhood; Children; Complications; complications (disease); Cotton; Cotton rat; Disease Models, Animal; Eosinophilia; Female; Glycoproteins; Human orthopneumovirus; Human subjects; Humoral immunity; Immune response; Immune system; Immunity; Immunity, Humoral; Immunoglobulins; infancy; infant diseases; Infants; Infections; Inflammatory response; Influenza; Interferon; interferon-gamma; Interferon-gamma - metabolism; Lung - virology; Lung diseases; Lungs; mice; neutralizing antibodies; Newcastle disease; Pneumonia; Proteins; Rats; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - administration & dosage; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus Vaccines - isolation & purification; Respiratory Syncytial Viruses - immunology; Respiratory Syncytial Viruses - isolation & purification; Respiratory tract diseases; Rodents; Sigmodon; Sigmodontinae; Time Factors; Upper airway; Vaccination; Vaccines; Viral infections; Viral Load; Virus-vectored; Viruses; Wheezing; γ-Interferon; Cotton rat; Inflammatory response; Respiratory syncytial virus; Virus-vectored; B cell memory; Upper airway
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2018.04.089

•A NDV-vectored RSV vaccine protects cotton rats from RSV challenge.•This vaccine induces long-lived neutralizing antibody.•This vaccine candidate can be used to immunize RSV immune animals. Human respiratory syncytial virus (RSV) is the leading cause of lower airway disease in infants worldwide and repeatedly infects immunocompetent individuals throughout life. Severe lower airway RSV infection during infancy can be life-threatening, but is also associated with important sequelae including development of asthma and recurrent wheezing in later childhood. The basis for the inadequate, short-lived adaptive immune response to RSV infection is poorly understood, but it is widely recognized that RSV actively antagonizes Type I interferon (IFN) production. In addition to the induction of the anti-viral state, IFN production during viral infection is critical for downstream development of robust, long-lived immunity. Based on the hypothesis that a vaccine that induced robust IFN production would be protective, we previously constructed a Newcastle disease virus-vectored vaccine that expresses the F glycoprotein of RSV (NDV-F) and demonstrated that vaccinated mice had reduced lung viral loads and an enhanced IFN-γ response after RSV challenge. Here we show that vaccination also protected cotton rats from RSV challenge and induced long-lived neutralizing antibody production, even in RSV immune animals. Finally, pulmonary eosinophilia induced by RSV infection of unvaccinated cotton rats was prevented by vaccination. Overall, these data demonstrate enhanced protective immunity to RSV F when this protein is presented in the context of an abortive NDV infection.