Oral Immunization with Recombinant Lactococcus lactis Expressing the Hemagglutinin of the Avian Influenza Virus Induces Mucosal and Systemic Immune Responses

Abstract

The aim of the study in this article is to explore a safe, convenient and effective oral mucosal vaccine candidate against highly pathogenic avian influenza. We have constructed an oral mucosal vaccine, LL36EH, by use of the genetically stable θ-replicating vector pMG36E, which expressed the fusion protein hemagglutinin 1 (HA(1)) in a live carrier, Lactococcus lactis MG1363. LL36EH was administered orally to mice three times at 2-week intervals. The specific serum IgG and mucosal IgA antibodies were detected and evaluated at different time points after immunization. The results showed that LL36EH could significantly induce specific anti-HA(1) IgA antibody in the intestine and specific anti-HA(1) IgG antibody in the serum (p < 0.05). Additionally, when the splenic lymphocytes isolated from immunized mice were stimulated by HA(1) antigen in vitro, splenic lymphocyte proliferative reaction and secretions of the cytokines IFN-γ and IL-4 were also significantly increased. Most importantly, the mice that were immunized with LL36EH were protected to some extent against lethal challenge of the H5N1 virus. LL36EH triggered the anti-HA(1)-specific humoral and cellular immune responses and protective immunity. Therefore, oral immunization with LL36EH could be a valuable strategy against highly pathogenic avian influenza for humans and animals.