ABSTRACT
Seasonal and pandemic influenzas are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. New RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent self-amplifying RNA (saRNA) vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/2013 H7N9. These saRNA vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The saRNA-NLC vaccines provided complete protection against morbidity and mortality in ferret challenge models, establishing this intranasally-administered saRNA-NLC vaccine platform as a potential pandemic response tool.
ONE SENTENCE SUMMARY A self-amplifying RNA-NLC vaccine, delivered intranasally, induces robust mucosal immunity in mice and protects against H5N1 and H7N9 in ferrets
Competing Interest Statement
AG and EAV declare no Competing Non-Financial Interests but the following Competing Financial Interests. AG and EAV are co-inventors on PCT patent application PCT/US21/40388, Co-lyophilized RNA and Nanostructured Lipid Carrier, and related national filings, as well as US provisional patent application 63/345,345, Intranasal Administration of Thermostable RNA Vaccines, and 63/144,169, A thermostable, flexible RNA vaccine delivery platform for pandemic response. All other authors declare that they have no competing interests.
