Development of Broadly Immunogenic and Universal Influenza Virus Vaccines

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Influenza viruses remain a major public health burden due to their ability to alter hemagglutinin (HA) epitopes. While conserved epitopes have been identified, there is still a fundamental gap in understanding how their structural presentation in vaccines influences immunogenicity and protection via immunization. In FY 2025, we studied the affects of distinct structural arrangements of trimeric HAs to modulate the breath of protection against influenza viruses of seasonal and pandemic origins. Using electron microscopy, biochemical analysis, and animal studies, we characterized HA complexes organized as lipid discs adorned with multiple trimeric spikes along their perimeters, which we termed spike nanobicelles (SNBs). Guided by these structural insights, we produced in vitro assembled SNBs (IA SNBs) from a classical H1N1 strain. Immunization with IA SNBs elicited broadly reactive pan-H1 antibodies and provided protection against antigenically divergent H1N1 viruses. Our findings show that viral glycoprotein spikes displayed as SNBs represent a promising vaccine platform that can address influenza antigenic variation and contribute to the development of universal influenza vaccines.