Heterosubtypic protection conferred by combined vaccination with M2e peptide and split influenza vaccine

There is urgent need to develop influenza vaccines with broad-spectrum protection against the potential influenza pandemic. The extracellular domain of influenza M2 protein (M2e) is considered as an appropriate target to induce heterosubtypic protection. We investigated the immunity and protection induced by combined vaccination with synthetic M2e peptide and traditional split influenza vaccine. The combined vaccination was able to induce similar strain-specific hemagglutinin inhibition (HI) antibodies as vaccination of split virus alone. However, aluminum-adjuvant but not oil-in-water-emulsion adjuvant combined vaccination was able to induce high titers of anti-M2e antibodies and provoke M2e-specific T lymphocyte response. Furthermore, we found that the addition of M2e peptide greatly enhanced the cross-protective efficacy of split virus in aluminum adjuvant but slightly weakened the efficacy of vaccination in oil-in-water-emulsion adjuvant. Moreover, aluminum-adjuvant combined vaccination conferred complete cross-protection against heterosubtypic influenza virus. According to the results, we suggest that the M2e peptide should be added into split influenza vaccine in the preparation for the potential influenza pandemic.