Fusion protein (M2e-HA2-NP) adjuvanted with γ-PGA/Alum induce the cross-reactivity against heterologous influenza A viruses

Abstract

Abstract The epidemic and pandemic influenza viruses result in substantial morbidity and mortality in humans. Vaccination is the most effective way to prevent influenza virus infection. In this study, we cloned the conserved regions of influenza A virus, extracellular domain of matrix protein 2 (M2e), hemagglutinin 2 (HA2) and nucleoprotein (NP). Then, we generated fusion (M2e-HA2-NP) protein as a universal vaccine antigen candidate. γ-PGA/Alum (PA) was used as an adjuvant to enhance the efficacy of fusion protein. In mice challenged with influenza viruses, fusion protein (15 μg) provided 100% protection against A/Puerto Rico/8/1934 (H1N1; PR8) or A/California/04/09 (pH1N1; CA04) and 80% protection against H3N2 (a reassortant virus carrying HA and NA genes of A/Hong Kong/1/68). In dose-sparing effect experiments, low dose (1 or 5 μg) of fusion protein with PA provided the same protection comparable to 15 μg of fusion protein against H1N1, pH1N1 and H3N2. Humoral and cellular immunities against heterologous influenza viruses were significantly enhanced in mice vaccinated with fusion protein mixed with PA compared with alum-adjuvanted fusion protein. Taken together, the fusion protein adjuvanted with PA may be a good vaccine candidate showing heterosubtypic cross-reactivity.