Sequence comparison between the extracellular domain of M2 protein human and avian influenza A virus provides new information for bivalent influenza vaccine design

To prevent the human and economic losses caused by human and avian influenza viruses, it is necessary to prepare safe bivalent influenza vaccines. Recent studies found that human influenza vaccines based on the extracellular domain of influenza M2 protein (M2e) induced broad-spectrum protective immunity in various antigen constructs. A prerequisite for using the M2e protein as a bivalent influenza vaccine component was to find out the sequence differences between human and non-human (avian or swine) influenza M2e proteins. Here, we completed such a comparison using 716 influenza M2e sequences available in Genbank. The results found one region on M2e protein consistent with host restriction specificities: PIRNEWGCRCN, PTRNGWECKCS and PIRNGWECRCN (aa10-20; the human, avian and swine specific M2e sequence, respectively). Interestingly, the comparison result was then validated by immunoblotting and enzyme-linked immunosorbent assay. The monoclonal antibody against the EVETPIRN sequence (aa6-13) of human M2e protein could weakly recognize avian M2e proteins bearing the EVETPTRN sequence (aa6-13) but failed to recognize avian M2e proteins bearing the EVETLTRN sequence (aa6-13). The data in this study provided useful information in the race to develop bivalent influenza vaccines against avian and human influenza A virus infection in human beings.