A recombinant protein containing highly conserved hemagglutinin residues 81-122 of influenza H5N1 induces strong humoral and mucosal immune responses.

Influenza has long been considered a serious global health threat. The highly pathogenic avian influenza A virus (IAV) H5N1, particularly the currently identified IAV/H7N9 in humans in China, illustrates that influenza is still a significant public health problem. Due to the high mortality of H5N1, development of safe and effective vaccines against divergent strains of H5N1 influenza virus, especially the one capable of inducing both strong systemic and local immune responses in the vaccinated targets, is a challenge of immediate importance. In the present study, we designed two recombinant proteins containing highly conserved hemagglutinin (HA) residues 81-122 of H5N1 fused with Fc of human IgG (HA-81-122-Fc) and/or foldon (Fd) trimeric motif (HA-81-122-Fdc), and identified their immunogenicity in vaccinated mice. We found that HA-81-122-Fc and HA-81-122-Fdc proteins formed high molecular weight dimer and oligomer, respectively, and induced potent IgG antibodies in vaccinated mouse sera and lung wash. Stronger IgG1 (Th2-associated) and IgG2 (Th1-associated) antibody responses could be raised in the sera of mice following last vaccination of HA-81-122-Fdc than those raised by HA-81-122-Fc vaccination. Importantly, HA-81-122-Fdc is able to elicit high titers of IgA antibodies in vaccinated mouse lung wash and sera through the parenteral immunization pathway. Our data demonstrated that the recombinant protein containing highly conserved HA residues 81-122 of H5N1 fused with Fd and Fc could induce strong local mucosal and systemic humoral immune responses in the vaccinated animals, revealing the possibility of developing an effective Fc-mediated mucosal influenza vaccine.