Influenza mRNA vaccine with engineered panhandle-forming UTRs provides potent protection against seasonal influenza viruses

Influenza is a highly contagious respiratory illness caused by influenza viruses, which remains a persistent challenge on global health. Vaccination is the most effective intervention to mitigate the public health burden caused by pandemic or endemic influenza. Compared to conventional vaccines, mRNA vaccines offer unprecedented advantages in prevention of infectious diseases. However, the optimization of mRNA vaccine design still remains a critical challenge. Herein, we report a novel engineered panhandle-forming untranslational region (UTR) derived from M gene segment of influenza A virus to enhance mRNA translational efficiency, innate immunogenicity, thus efficacy. In mouse model, vaccination with influenza HA mRNA vacccine carrying engineered UTRs elicited potent innate immunity, robust cellular and humoral immunity as low as dose of 0.1 ug per mouse. Furthermore, it also conferred effective protection against challenge with seasonal influenza viruses.This  highlight the benefit of panhandle structures of UTR in amplifying translation, innate and adaptive immunogenicity of mRNA vaccines.

Junwi Li, PhD, Professor. Previously, he/she was a postdoctoral fellow at the University of Saskatchewan in Canada, a postdoctoral fellow at Texas Tech University in the United States, and a researcher at the University of Pennsylvania. Research areas include mRNA vaccines, universal influenza vaccines, live attenuated influenza vaccines, vector influenza vaccines, and bacterial toxin vaccines; novel vaccine formulations; replication mechanisms of Ebola virus, rabies virus, and influenza virus; screening of anti-influenza and anti-Ebola drugs; development of animal models for virus research; and screening and applications of tumor neoantigens.