Broad-spectrum vaccine via combined immunization routes triggers potent immunity to SARS-CoV-2 and its variants

Developing broad-spectrum vaccines and optimal vaccination strategies is crucial to controlling the COVID-19 pandemic. Here, we generated a chimpanzee adenoviral vector-based COVID-19 vaccine carrying broad-spectrum immunogens, modified full-length spike, and conserved T-cell epitopes of SARS-CoV-2, and assessed its immune response in mice through intramuscular (i.m.), intranasal (i.n.), or combined immunization routes (i.m. + i.n., or i.n. + i.m.). Compared to other vaccination strategies, the two combined regimens elicited higher neutralizing antibody (NAb) responses to all variants. Compared to i.n. + i.m. regimen, the i.m. + i.n. regimen stimulated a stronger secondary GC response, which is more pivotal to high-quality antibody production than the primary GC response. Moreover, the i.m. + i.n. regimen was adept at mediating systemic cellular immunity, while the i.n. + i .m. regimen tended to elicit lung tissue-resident memory T (T-RM) cell responses. Overall, the two combined regimens induced comprehensive but distinct immune responses consisting of lgA, lgG, NAbs, GC B cells, long-lived plasma cells, TRM cells, and systemic memory T cells, which conferred complete protection against BA.2 infection in hACE2 transgenic mice, and warranted further investigation as potential universal vaccination strategies.

Automated summary

Developing broad-spectrum vaccines and optimal vaccination strategies is crucial to controlling the COVID-19 pandemic. In this study, a chimpanzee adenoviral vector-based COVID-19 vaccine was generated and its immune response was assessed in mice through different immunization routes. The results showed that the combined immunization routes elicited higher neutralizing antibody responses and induced comprehensive but distinct immune responses. This vaccine shows potential as a universal vaccination strategy.