Recombinant probiotic Escherichia coli delivers the polymeric protein of swine influenza virus for protection

Swine influenza virus invades the host through the respiratory mucosa, which severely restricts the development of the pig breeding industry. To construct monomeric and trimeric vaccines, we developed recombinant Escherichia coli Nissle 1917 (EcN) strains that express the receptor binding site (RBS) of the hemagglutinin (HA) antigen from H1N1 swine influenza virus. After the mucosal immunization of mice, we found that probiotics activated CD40 and CD86 in DCs and increased the levels of IL-4 and IFN-γ secretion by T cells. Furthermore, the probiotics improved the function of the mucosal immune system, increased the level of SIgA, level of IgG and number of B220⁺IgA⁺, and activated germinal center B cells. The challenge experiment revealed that the probiotics alleviated weight loss, reduced pathological injury to the lungs, and protected the mice from virus infection. We also observed that the serum neutralizing antibodies of immunized piglets significantly increased, which reduced the shedding frequency of swine influenza virus in the nose of the piglets and reduced the pathological damage by activating the T cell immune response in infected piglets. Thus, the constructed probiotics are promising candidates for effective non-traditional swine influenza vaccines.