Development of a vaccine to attenuate viral exacerbation of asthma (P4276)

Abstract

Abstract Viral exacerbation of asthma exacerbation is a major cause of emergency department visits and hospitalization. Thus, vaccination against causative viruses would be an effective method for the attenuation of viral exacerbation for asthmatics. Because live/attenuated vaccines are not safe for asthmatics, inactivated viral vaccines need to be developed. We hypothesize that the innate immune response produces pro-inflammatory signals that determine the outcome of the adaptive immune response. We are evaluating the potential of an intranasal inactivated respiratory syncytial virus vaccine consisting of inactivated virus in conjunction with liposome (delivery agent) and TLR agonists (immune stimulatory agent) to attenuate viral asthma exacerbation. In vitro, bone marrow dendritic cells stimulated with inactivated RSV and TLR7/9 agonists induced more CXCL10, IFNβ, and DLL4 compared to inactivated RSV alone. In vivo, mice vaccinated with liposome-RSV and TLR 7/9 agonists enhanced viral clearance, without inducing an IL-33 or IL-17a response. Using a cockroach allergen RSV-exacerbated asthma mouse model, vaccinated mice had reduced viral load and increased activated lymphocytes and RSV specific antibodies. However, mucus secretion was also increased, indicating that further refining of the vaccine will be necessary. However, our data indicate successful vaccination against a virus clinically associated with asthma exacerbation in a well-defined animal model of asthma.