M2e-Based Universal Influenza A Vaccines

Overview

Journal Vaccines (Basel)

Date 2015 Sep 8

PMID 26344949

Citations 89

Authors

Lei Deng

Ki Joon Cho

Walter Fiers

Xavier Saelens

Affiliations

Soon will be listed here.

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.

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References

Turley C, Rupp R, Johnson C, Taylor D, Wolfson J, Tussey L . Safety and immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4xM2e) in healthy adults. Vaccine. 2011; 29(32):5145-52. DOI: 10.1016/j.vaccine.2011.05.041. View

Jegerlehner A, Schmitz N, Storni T, Bachmann M . Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. J Immunol. 2004; 172(9):5598-605. DOI: 10.4049/jimmunol.172.9.5598. View

Schotsaert M, Ysenbaert T, Neyt K, Ibanez L, Bogaert P, Schepens B . Natural and long-lasting cellular immune responses against influenza in the M2e-immune host. Mucosal Immunol. 2012; 6(2):276-87. DOI: 10.1038/mi.2012.69. View

Grandea 3rd A, Olsen O, Cox T, Renshaw M, Hammond P, Chan-Hui P . Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. Proc Natl Acad Sci U S A. 2010; 107(28):12658-63. PMC: 2906546. DOI: 10.1073/pnas.0911806107. View

Webster R, BEAN W, Gorman O, Chambers T, Kawaoka Y . Evolution and ecology of influenza A viruses. Microbiol Rev. 1992; 56(1):152-79. PMC: 372859. DOI: 10.1128/mr.56.1.152-179.1992. View

Bodewes R, Kreijtz J, Rimmelzwaan G . Yearly influenza vaccinations: a double-edged sword?. Lancet Infect Dis. 2009; 9(12):784-8. DOI: 10.1016/S1473-3099(09)70263-4. View

Heinen P, de Boer-Luijtze E, Bianchi A . Respiratory and systemic humoral and cellular immune responses of pigs to a heterosubtypic influenza A virus infection. J Gen Virol. 2001; 82(Pt 11):2697-2707. DOI: 10.1099/0022-1317-82-11-2697. View

Ameiss K, Ashraf S, Kong W, Pekosz A, Wu W, Milich D . Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by recombinant attenuated Salmonella displaying a delayed lysis phenotype. Vaccine. 2010; 28(41):6704-13. PMC: 2939226. DOI: 10.1016/j.vaccine.2010.07.083. View

Petukhova N, Gasanova T, Stepanova L, Rusova O, Potapchuk M, Korotkov A . Immunogenicity and protective efficacy of candidate universal influenza A nanovaccines produced in plants by Tobacco mosaic virus-based vectors. Curr Pharm Des. 2013; 19(31):5587-600. DOI: 10.2174/13816128113199990337. View

10.

Reese K, Lupfer C, Johnson R, Mitev G, Mullen V, Geller B . A Novel Lactococcal Vaccine Expressing a Peptide from the M2 Antigen of H5N2 Highly Pathogenic Avian Influenza A Virus Prolongs Survival of Vaccinated Chickens. Vet Med Int. 2013; 2013:316926. PMC: 3674685. DOI: 10.1155/2013/316926. View

11.

Fan J, Liang X, Horton M, Perry H, Citron M, Heidecker G . Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Vaccine. 2004; 22(23-24):2993-3003. DOI: 10.1016/j.vaccine.2004.02.021. View

12.

Johnson N, Mueller J . Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic. Bull Hist Med. 2002; 76(1):105-15. DOI: 10.1353/bhm.2002.0022. View

13.

Wolf A, Mozdzanowska K, Williams K, Singer D, Richter M, Hoffmann R . Vaccination with M2e-based multiple antigenic peptides: characterization of the B cell response and protection efficacy in inbred and outbred mice. PLoS One. 2011; 6(12):e28445. PMC: 3236751. DOI: 10.1371/journal.pone.0028445. View

14.

McCown M, Pekosz A . Distinct domains of the influenza a virus M2 protein cytoplasmic tail mediate binding to the M1 protein and facilitate infectious virus production. J Virol. 2006; 80(16):8178-89. PMC: 1563831. DOI: 10.1128/JVI.00627-06. View

15.

Zhao G, Lin Y, Du L, Guan J, Sun S, Sui H . An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. Virol J. 2010; 7:9. PMC: 2823673. DOI: 10.1186/1743-422X-7-9. View

16.

Nair H, Brooks W, Katz M, Roca A, Berkley J, Madhi S . Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet. 2011; 378(9807):1917-30. DOI: 10.1016/S0140-6736(11)61051-9. View

17.

Talbot H, Rock M, Johnson C, Tussey L, Kavita U, Shanker A . Immunopotentiation of trivalent influenza vaccine when given with VAX102, a recombinant influenza M2e vaccine fused to the TLR5 ligand flagellin. PLoS One. 2011; 5(12):e14442. PMC: 3010987. DOI: 10.1371/journal.pone.0014442. View

18.

Xu R, Ekiert D, Krause J, Hai R, Crowe Jr J, Wilson I . Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science. 2010; 328(5976):357-60. PMC: 2897825. DOI: 10.1126/science.1186430. View

19.

Grambas S, Hay A . Maturation of influenza A virus hemagglutinin--estimates of the pH encountered during transport and its regulation by the M2 protein. Virology. 1992; 190(1):11-8. DOI: 10.1016/0042-6822(92)91187-y. View

20.

Matsuzaki Y, Katsushima N, Nagai Y, Shoji M, Itagaki T, Sakamoto M . Clinical features of influenza C virus infection in children. J Infect Dis. 2006; 193(9):1229-35. DOI: 10.1086/502973. View