Vaccination with recombinant 4×M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens

Immunogenicity and protective efficacy of the norovirus P particle-M2e chimeric vaccine in chickens

“…The constructed vaccine, especially in tetrameric form, showed significant reduction in virus shedding against H5N2 LPAI virus challenge [25]. Most recently, vaccination of chickens with four copies of M2e linked to Mycobacterium tuberculosis HSP70 were shown to enhance both humoral and cell-mediated immune responses and reduce viral shedding against H9N2 LPAI virus challenge [18].…”

“…Comparison of M2e sequence from different human, swine and avian viruses revealed that N-terminal amino acids are identical among these viruses and only 5 amino acids at position 10-20 were found to be host specific [16]. Because M2e is small in size and poorly immunogenic, several approaches were developed to increase its immunogenicity including: fusion of the M2e peptide to the Hepatitis B virus core protein [17] or Heat Shock Protein-70 of M. tuberculosis [18,19], and expression through influenza viruslike particles [20]. These constructs have induced an immune response against M2e which in turn showed varying degrees of protection in different animal models against different challenge strains.…”

A truncated C-terminal fragment of Mycobacterium tuberculosis HSP70 enhances cell-mediated immune response and longevity of the total IgG to influenza A virus M2e protein in mice

“…According to the results of our previous studies Dabaghian et al, 2014;Jazi et al, 2012), it is expected that provided full protection, less sever weight loss and moderate clinical signs can be explained by the mechanism in which r4M2e.HSP70c might modulate disease severity by decreasing viral replication and enhance viral clearance (Schotsaert et al, 2013). In this mechanism, natural viral infection could replicate in body at a low level and adaptive immune system could be established against infection and provide sterilizing immunity.…”

“…In that, mHSP70c significantly enhanced the M2e-based vaccine potency against hetro-or homosubtypic (H1N1, H3N2, or H9N2) influenza infection in Balb/C mice after a prime-boost vaccination regimen . However, that study was limited by the lack of antibody isotyping analysis and cytokine data, but the potency and protectivity of the r4M2e.HSP70c fusion protein was recently evaluated in chicken in detail (Dabaghian et al, 2014). In which, vaccination with the r4M2e.HSP70c fusion protein promoted an enhanced cellular immune responses characterized by increased levels of Th1-type (IFN-c) and Th2-type (IL-4) cytokines production and increased CD4+ to CD8+ ratios (Dabaghian et al, 2014).…”

“…Previously, we have demonstrated that four tandem repeats of influenza A virus M2e genetically fused to the C-terminus of the Mycobacterium tuberculosis HSP70 (mHSP70c), which was expressed in Escherichia coli as a recombinant 4M2e.HSP70c fusion protein significantly enhanced the recombinant M2e-based vaccine potency in chickens and Balb/C mice after a prime-boost vaccination regimen (Dabaghian et al, 2014;Jazi et al, 2012).…”