Ever since the 1918 Flu pandemic, we have suffered three more Influenza virus pandemics resulting in substantial public health and socio-economic burden. Given the rapid genetic shift of zoonic influenza viruses, we still face difficulties maintaining the effectiveness of seasonal influenza virus vaccines especially in the context of controlling viruses with pandemic potential. This warrants the need for a “Universal influenza vaccine” which would protect vaccine recipients from influenza viruses.
My research in the García-Sastre lab involves the formulation of a second-generation trivalent live attenuated influenza vaccine (LAIV) along with the development of methodologies for the development of influenza vaccines.
This project involves the use of attenuated influenza viruses which lack the interferon antagonist non-structural protein 1 (NS1) while retaining the nuclear export protein (NEP). We have developed chimeric hemagglutinin (HA) constructs which consist of exotic HA heads while maintaining a more conserved common stalk domain in order to direct immune responses against the stalk portion which has been shown to induce neutralizing antibodies. By combining both platforms together, we intend to device a LAIV vaccine and the pre-clinical trail experiments will be conducted in a mouse model and ferrets using representative challenge viruses along with highly pathogenic BSL-3 category level pathogens. This effort in done in collaboration with our industry partners, Vivaldi-Biosciences.
A growing body of scientific evidence has shown the effectiveness of NA based vaccines and therefore I am exploring the possibilities of extracting catalytically active NA heads which can be used as a source of antigen for NA based vaccine. We have developed viruses harboring proteolytic cleavage sequences which can be processed to obtain catalytically active NA heads.
Salvatore, M., Rathnasinghe, R et al (2020). Increased interferon mediated antiviral response In vivo by prophylactic treatment using an influenza A virus lacking the NS1 gene. NPJ Vaccines. *Preparing to submit
Rathnasinghe, R.*, Kaul, D*(2020). Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in humans and ferrets. Nature communications. *Under review
Mena, J., Brito, B., Moreira, R., Tadich, T., Gonzales, I., Rathnasinghe, R., et al. (2018) Reemergence of H3N8 equine influenza A virus in Chile. Transboundary and emerging diseases
Le corre., N, Martinez-Valdebenito., C, Barriga, F., Contreras., Garcia, T., Rathnasinghe., R et al (2018). Circulating T Follicular Helper Cells and Immune Response Induced by Influenza Vaccine in Children with Acute Lymphoblastic Leukemia During Maintenance Therapy. Open Forum Infectious Diseases