Matrix Protein 2 Vaccination and Protection against Influenza Viruses, Including Subtype H5N1

Abstract

Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing fulllength consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.

Evaluation of the protection induced by avian influenza vaccines containing a 1994 Mexican H5N2 LPAI seed strain against a 2008 Egyptian H5N1 HPAI virus belonging to clade 2.2.1 by means of serological andin vivotests

“…This may also suggest that cellular immunity plays a more important role in AI vaccination efficacy than originally thought (Khalenkov et al, 2009). Both the former and the latter have been described to play a role in protecting mammalian species such as mice (Tompkins et al, 2007;Zhirnov et al, 2007) and ferrets (Price et al, 2009).…”

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

“…To demonstrate that virus-specific T-cell responses not only correlated with protection but were also directly responsible for heterosubtypic immunity, we performed adoptive transfer experiments. Although protective antibodies have been described that are specific for conserved epitopes in the stem region of the HA molecule (Corti et al, 2010;Ekiert et al, 2009;Steel et al, 2010;Wang et al, 2010), the matrix-2 protein (Fan et al, 2004;Heinen et al, 2002;Slepushkin et al, 1995;Song et al, 2011;Tompkins et al, 2007) and the nucleoprotein LaMere et al, 2011a, b;RangelMoreno et al, 2008), the transfer of serum obtained from mice infected with sH3N2 virus failed to protect against infection with heterologous pH1N1 virus. Either antibodies to these conserved epitopes were not induced or the titres were too low to be protective.…”

Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses

“…Monoclonal antibodies to M2e have been shown to be protective in vivo (13)(14)(15)(16)(17), and several groups have demonstrated protection against infection with vaccine strategies based on M2e (18)(19)(20)(21)(22)(23). In these cases, purified M2 protein or peptides derived from M2e sequence have been used as immunogens to generate antiM2e antibodies in animals or as vaccine candidates.…”