Abstract
The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine.
Highlights
Current influenza vaccines based on influenza virus surface glycoprotein hemagglutinin (HA) antigens are effective if the predicted vaccine strains and circulating viruses are to be wellmatched
It has been reported that the cross-reactivity of antibodies induced by M2 ectodomain (M2e)-carrier constructs based on consensus M2e sequences with complete Freund’s adjuvant were determined against several M2e peptides, and no or low cross-reactivity was observed with avian M2e peptides that differed by 3 to 4 aa from the consensus sequence [11, 39]
In order to overcome heterogeneity of M2e among influenza A viruses, we expressed in yeast cells a genetically designed vaccine construct with tandem repeat of M2e consisting of representative M2e sequences from human, swine, and avian influenza viruses
Summary
Current influenza vaccines based on influenza virus surface glycoprotein hemagglutinin (HA) antigens are effective if the predicted vaccine strains and circulating viruses are to be wellmatched. It is difficult to predict potential pandemic strains. The emergence of the swine-origin 2009 H1N1 pandemic virus explicitly demonstrated how current influenza vaccination was not effective in controlling a new pandemic [1]. Avian influenza viruses such as H5, H7, and H9 subtypes continue to circulate in nature, raising serious concerns for their possibility of sustained human-to-human transmission [2, 3]. Development of effective vaccines conferring a broad range of cross protection is considered to be of high priority.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
