Abstract
BackgroundThe development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal.ResultsLactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1.ConclusionsL. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.
Highlights
The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal
L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application
A consistently high expression level of the HA1-M2 protein was observed on the L. lactis/pNZ8149-HA1-M2 cells (Fig. 1c, right panel), and no specific fluorescence signals were detected on the L. lactis/pNZ8149 cells (Fig. 1c, left panel)
Summary
The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. The currently licensed inactivated influenza virus vaccines for poultry are whole viruses or disrupted viral antigens containing hemagglutinin and neuraminidase glycoproteins, which are the major targets of neutralizing antibodies [3, 4] These vaccines that are based on neutralizing antibody responses to the highly variable influenza HA protein provide protection against only homologous but not antigenically distinct heterologous viruses [5]. To enhance the immunogenicity of M2e, some strategies have been reported for immunization with M2e peptide fusion constructs linked to carrier vehicles as vaccine candidates, which have been shown to have safety issues but provide protection against lethal infection in chickens [8, 9] These M2e vaccine candidates provide limited protection against lethal challenge, as shown by significant weight loss and signs of disease, even in the presence of potent adjuvants, such as heatlabile endotoxin or cholera toxin, Freund adjuvants, or
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