Mohammed Y E Chowdhury1,2, Rui Li1, Jong-Soo Lee1 and Chul-Joong Kim1
Posters-Accepted Abstracts: Virol-mycol
To develop a safe and effective mucosal vaccine against influenza A viruses, gene construct of the highly conserved matrix protein-2 (sM2) and fusion peptide of hemagglutinin (HA2) were successfully joined to the well-known mucosal adjuvant cholera toxin subunit A1 (CTA1). It is possible that the intranasal administration of the recombinant fusion protein sM2HA2 or the recombinant fusion protein resulting from joining gene constructs encoding sM2HA2 and CTA1-conjugated sM2HA2 (sM2HA2CTA1) using 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, could induce a high degree of systemic immunity (IgG and IgA) at the site of inoculation as well as at remote locations. The mucosal administration of sM2HA2CTA1/PC NPs may also significantly increase the levels of sM2- or HA2-specific cell-mediated immunity because increased release of both IFN-γ and IL-4 was observed.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 better protection against lethal challenges compared with sM2HA2 and sM2HA2CTA1 without PC NPs. Thus, sM2HA2CTA1/PC NPs may be a promising mucosal vaccine candidate against pandemic influenza.
