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

tetano

Editor, Senior Moderator
Emerg Microbes Infect. 2019;8(1):45-54. doi: 10.1080/22221751.2018.1558962.
[h=1]Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine.[/h] Yao Y[SUP]1,[/SUP][SUP]2[/SUP], Wang H[SUP]3[/SUP], Chen J[SUP]4[/SUP], Shao Z[SUP]2[/SUP], He B[SUP]2[/SUP], Chen J[SUP]2[/SUP], Lan J[SUP]5[/SUP], Chen Q[SUP]4[/SUP], Chen Z[SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.


[h=4]KEYWORDS:[/h] Influenza; M2e; Universal influenza vaccine; optimized M2e DNA vaccine; tPA

PMID: 30866759 DOI: 10.1080/22221751.2018.1558962
 
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