Article ID Journal Published Year Pages File Type
5545137 Veterinary Microbiology 2017 12 Pages PDF
Abstract

•Construction of poly-γ-glutamic acid (γ-PGA)-chitosan nanoparticles (PC NPs) containing conserved antigens of Influenza virus and mucosal adjuvant cholera toxin subunit A1 (CTA1) as a safe and effective mucosal vaccine against emerging influenza A viruses.•The mucosal administration of sM2HA2CTA1/PC NPs could induce a high degree of systemic, mucosal and cell-mediated immune response.•Induced immune responses could protect mice against 10MLD50 of divergent influenza subtypes.•The immune response and efficacy of protection was maintained up to six months after final inoculation.

To develop a safe and effective mucosal vaccine that broad cross protection against seasonal or emerging influenza A viruses, we generated a mucosal influenza vaccine system combining the highly conserved matrix protein-2 (sM2), fusion peptide of hemagglutinin (HA2), the well-known mucosal adjuvant cholera toxin subunit A1 (CTA1) and poly-γ-glutamic acid (γ-PGA)-chitosan nanoparticles (PC NPs), which are safe, natural materials that are able to target the mucosal membrane as a mucosal adjuvant. The mucosal administration of sM2HA2CTA1/PC NPs could induce a high degree of systemic immunity (IgG and IgA) at the site of inoculation as well as at remote locations and also significantly increase the levels of sM2- or HA2-specific cell-mediated immune response. In challenge tests in BALB/c mice with 10 MLD50 of A/EM/Korea/W149/06(H5N1), A/Puerto Rico/8/34(H1N1), A/Aquatic bird/Korea/W81/2005(H5N2), A/Aquatic bird/Korea/W44/2005 (H7N3) or A/Chicken/Korea/116/2004(H9N2) viruses, the recombinant sM2HA2CTA1/PC NPs provided cross protection against divergent lethal influenza subtypes and also the protection was maintained up to six months after vaccination. Thus, sM2HA2CTA1/PC NPs could be a promising strategy for a universal influenza vaccine.

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