Host-targeted self-attenuated influenza virus as an effective prophylactic vaccine in young ages 2245

Abstract Description Influenza is still a global public health problem for children despite a vigorous campaign for influenza vaccination in many countries. The recent emergence of COVID-19 can also complicate influenza in children and make it more desirable to vaccinate young children against influenza. We have recently constructed a new live attenuated influenza virus, named host-targeted self-attenuated influenza virus (SAIV), which can express a functional artificial microRNA (amiRNA). The expression of the amiRNA can inhibit the expression of a host gene, Cdc2-like kinase 1 (CLK1), that is critical for virus replication, and therefore the resultant recombinant virus is replication-restricted and attenuated in host cells. This host-targeted SAIV was produced in embryonic chicken eggs and evaluated in a young Balb/c mouse model of influenza infection. As a prophylactic vaccine, a single dose of intranasal vaccination with this SAIV in 3-week-old mice elicited robust antibody and T cell responses against influenza and demonstrated significant protective immunity against lethal challenge with wild-type influenza virus (PR8, H1N1). Our research finding has shown proof of concept that the host-targeted SAIV vaccine can be further developed as an effective influenza vaccine in young ages. Funding Sources Supported by research grants from National Institute of Allergy and Infectious Diseases (AI133207) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD109732). Topic Categories Vaccines and Immunotherapy (VAC)