Self-adjuvant multiepitope nanovaccine based on ferritin induced long-lasting and effective mucosal immunity against H3N2 and H1N1 viruses in mice.

The influenza A virus (IAV) is a ubiquitous and continuously evolving respiratory pathogen. The intranasal vaccination mimicking natural infections is an attractive strategy for controlling IAVs. Multiepitope vaccines accurately targeting multiple conserved domains have the potential to broaden the protective scope of current seasonal influenza vaccines and reduce the risk of generating escape mutants. Here, multiple linear epitopes from the matrix protein 2 ectodomain (M2e) and the hemagglutinin stem domain (HA2) are fused with the Helicobacter pylori ferritin, a self-assembled nanocarrier and mucosal adjuvant, to develop a multiepitope nanovaccine. Through intranasal delivery, the prokaryotically expressed multiepitope nanovaccine elicits long-lasting mucosal immunity, broad humoral immunity, and robust cellular immunity without any adjuvants, and confers complete protection against H3N2 and H1N1 subtypes of IAV in mice. Importantly, this intranasal multiepitope nanovaccine triggers memory B-cell responses, resulting in secretory immunoglobulin A (sIgA) and serum immunoglobulin G (IgG) levels persisting for more than five months post-immunization. Therefore, this intranasal ferritin–based multiepitope nanovaccine represents a promising approach to combating respiratory pathogens. [Display omitted] • Developed an intranasal multiepitope influenza nanovaccine using the Helicobacter pylori ferritin nanoplatform. • The Helicobacter pylori ferritin is a safe and effective mucosal adjuvant. • Insertion of up to 170 amino acids does not affect the self-assembly ability of ferritin in Escherichia coli. • Mucosal immunity induced by the multiepitope nanovaccine lasts for 6 months. • The intranasal nanovaccine represents a compelling strategy against respiratory pathogens. [ABSTRACT FROM AUTHOR]