posted on 2023-12-12, 12:06authored byJaeyoung Park, Julie A. Champion
There remains a need
for the development of a universal influenza
vaccine, as current seasonal influenza vaccines exhibit limited protection
against mismatched, mutated, or pandemic influenza viruses. A desirable
approach to developing an effective universal influenza vaccine is
the incorporation of highly conserved antigens in a multivalent scaffold
that enhances their immunogenicity. Here, we develop a broadly cross-reactive
influenza vaccine by functionalizing self-assembled protein nanocages
(SAPNs) with multiple copies of the hemagglutinin stalk on the outer
surface and matrix protein 2 ectodomain on the inner surface. SAPNs
were generated by engineering short coiled coils, and the design was
simulated by MD GROMACS. Due to the short sequences, off-target immune
responses against empty SAPN scaffolds were not seen in immunized
mice. Vaccination with the multivalent SAPNs induces high levels of
broadly cross-reactive antibodies of only external antigens, demonstrating
tight spatial control over the designed antigen placement. This work
demonstrates the use of SAPNs as a potential influenza vaccine.