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M2e-Based Universal Influenza A Vaccines.

Deng L, Cho KJ, Fiers W, Saelens X - Vaccines (Basel) (2015)

Bottom Line: The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine.We address the mechanism of action and the clinical development of M2e-vaccines.Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.

View Article: PubMed Central - PubMed

Affiliation: Inflammation Research Center, VIB, Technologiepark 927, B-9052 Ghent, Belgium. Lei.deng@dmbr.vib-ugent.be.

ABSTRACT
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.

No MeSH data available.


Related in: MedlinePlus

M2 from PR8 virus with the identified human T cell epitopes underlined.
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vaccines-03-00105-f002: M2 from PR8 virus with the identified human T cell epitopes underlined.

Mentions: M2-specific T cell responses have been described in humans [60,61]. The human CD4 and CD8 CTL epitopes directed against M2 that have been defined experimentally and are shown in Figure 2 [60,62,63]. We reported the presence of an major histocompatibility complex (MHC) class II restricted T cell epitope in M2e, that is restricted to BALB/c mouse strains (H-2d) and was strongly induced by mucosal vaccination by means of the recombinant protein CTA1-M2e-DD [64]. The CD4 T cell epitopes in M2e have been mapped for the mouse. Pejoski et al. found that M2e2-16 (SLLTEVETPIRNEWG) peptide contains only B cell epitopes but no T cell epitope, which explains why immunization with M2e2-16 peptide formulated in Freund’s adjuvant failed to induce antibody responses against M2e as present on virus particles. However, by including a chemically conjugated T helper epitope derived from HA in the M2e conjugate, M2e specific antibodies were readily generated [65]. In line with this, we reported that immunization with the N-terminal nine amino acids residue of M2e (SLLTEVETP) coupled to keyhole limpet haemocyanin (KLH) induced very low M2e-specific IgG responses [66].


M2e-Based Universal Influenza A Vaccines.

Deng L, Cho KJ, Fiers W, Saelens X - Vaccines (Basel) (2015)

M2 from PR8 virus with the identified human T cell epitopes underlined.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494237&req=5

vaccines-03-00105-f002: M2 from PR8 virus with the identified human T cell epitopes underlined.
Mentions: M2-specific T cell responses have been described in humans [60,61]. The human CD4 and CD8 CTL epitopes directed against M2 that have been defined experimentally and are shown in Figure 2 [60,62,63]. We reported the presence of an major histocompatibility complex (MHC) class II restricted T cell epitope in M2e, that is restricted to BALB/c mouse strains (H-2d) and was strongly induced by mucosal vaccination by means of the recombinant protein CTA1-M2e-DD [64]. The CD4 T cell epitopes in M2e have been mapped for the mouse. Pejoski et al. found that M2e2-16 (SLLTEVETPIRNEWG) peptide contains only B cell epitopes but no T cell epitope, which explains why immunization with M2e2-16 peptide formulated in Freund’s adjuvant failed to induce antibody responses against M2e as present on virus particles. However, by including a chemically conjugated T helper epitope derived from HA in the M2e conjugate, M2e specific antibodies were readily generated [65]. In line with this, we reported that immunization with the N-terminal nine amino acids residue of M2e (SLLTEVETP) coupled to keyhole limpet haemocyanin (KLH) induced very low M2e-specific IgG responses [66].

Bottom Line: The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine.We address the mechanism of action and the clinical development of M2e-vaccines.Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.

View Article: PubMed Central - PubMed

Affiliation: Inflammation Research Center, VIB, Technologiepark 927, B-9052 Ghent, Belgium. Lei.deng@dmbr.vib-ugent.be.

ABSTRACT
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.

No MeSH data available.


Related in: MedlinePlus