posted on 2023-11-21, 23:03authored byKeegan Braz Gomes, Yi-Nan Zhang, Yi-Zong Lee, Mor Eldad, Alexander Lim, Garrett Ward, Sarah Auclair, Linling He, Jiang Zhu
The development of a cross-protective pan-influenza A
vaccine remains
a significant challenge. In this study, we designed and evaluated
single-component self-assembling protein nanoparticles (SApNPs) presenting
the conserved extracellular domain of matrix protein 2 (M2e) as vaccine
candidates against influenza A viruses. The SApNP-based vaccine strategy
was first validated for human M2e (hM2e) and then applied to tandem
repeats of M2e from human, avian, and swine hosts (M2ex3). Vaccination
with M2ex3 displayed on SApNPs demonstrated higher survival rates
and less weight loss compared to the soluble M2ex3 antigen against
the lethal challenges of H1N1 and H3N2 in mice. M2ex3 I3-01v9a SApNPs
formulated with a squalene-based adjuvant were retained in the lymph
node follicles over 8 weeks and induced long-lived germinal center
reactions. Notably, a single low dose of M2ex3 I3-01v9a SApNP formulated
with a potent adjuvant, either a Toll-like receptor 9 (TLR9) agonist
or a stimulator of interferon genes (STING) agonist, conferred 90%
protection against a lethal H1N1 challenge in mice. With the ability
to induce robust and durable M2e-specific functional antibody and
T cell responses, the M2ex3-presenting I3-01v9a SApNP provides a promising
pan-influenza A vaccine candidate.