Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine

Abstract

Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.

Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study

“…Therefore, HA2 attracted considerable interest for developing a universal vaccine for influenza virus [1]. On the other hand, the M2 antigen has a fragment in its N-terminal region that is highly conserved in almost all influenza virus subtypes [24]. The only disadvantage of M2e is its low immunogenicity, therefore, needs to be used with adjuvants to improve M2e-based vaccines immunogenicity [25].…”

Universal anti-influenza vaccines based on viral HA2 and M2e antigens

“…For more effective presentation of M2e to the immune cells and higher activation of humoral and T-cell immunity, viral vectors based on baculoviruses (Black et al, 1993;Slepushkin et al, 1995), papaya mosaic virus (PapMV) (Denis et al, 2008), vaccinia viruses (Hessel et al, 2014) and adenoviruses (Coughlan et al, 2015) have been utilized as antigen carriers. Promising method 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 for elicitation of a robust immune response is also DNA vaccination with plasmid DNA that comprises genetic information for M2e (Yao et al, 2019). Another option is represented by adjuvant substances applied together with the immunogen (Eliasson et al, 2008) or carriers such as KLH (Fan et al, 2004;De Filette et al, 2011), nanoparticles, and (or?)…”

Flu Universal Vaccines: New Tricks on an Old Virus

“…Although the natural M2e has low immunogenicity and abundance, a M2e-specific and protective monoclonal antibody 14C2 has been isolated early (Zebedee and Lamb 1989 ; Treanor et al 1990 ). Therefore this region has since been extensively evaluated as a promising immunogen for universal influenza vaccines (Farahmand et al 2019 ; Yao et al 2019 ).…”