Intranasal administration with recombinant Bacillus subtilis induces strong mucosal immune responses against pseudorabies

Abstract

Background Pseudorabies caused by pseudorabies virus (PRV) mainly infects the swine and seriously threatens the biosafety of the other animals, including humans. Since 2011, the outbreaks of PRV mutants have caused enormous economic losses in the swine industry, and traditional vaccines cannot offer enough protection. PRV can transmit by direct contact, aerosol transmission and pollutants. PRV mainly transmit through the nasal mucosa. After infecting the nasal epithelial cells, PRV can quickly infect the olfactory nerve and establish a potential infection of sensory neurons. Therefore, nasal immunity can effectively prevent viral colonization infection. Recombinant Bacillus subtilis has been widely used to deliver antigen and achieve adequate protective immune responses. Results The present study successfully constructed recombinant Bacillus subtilis ( B. subtilis ) expressing the dominant antigen regions of PRV gC and gD proteins (named B. subtilis -gCa and B. subtilis -gDa). Furtherly, we evaluated the immunogenicity of the two recombinant B. subtilis in mice. The mice intranasal administration with B. subtilis -gCa and B. subtilis -gDa effectively stimulated IgA and IgG immune responses, further regulated specific T lymphocytes proliferative response by IFN-γ and IL-10, and ultimately produced high titers of neutralizing antibodies against PRV infection. In particular, B. subtilis -gDa possessed more excellent immune effect than B. subtilis -gCa in mice. Conclusions These results suggested that B. subtilis -gCa and B. subtilis -gDa could trigger high levels of mucosal and systemic immune responses and would be potential candidates for developing PRV vaccines. Electronic supplementary material The online version of this article (10.1186/s12934-019-1151-8) contains supplementary material, which is available to authorized users.

Current Status and Challenge of Pseudorabies Virus Infection in China

“…Fantastically, the latest research showed that using Bacillus subtilis as a recombinant vaccine expressing PRV gC and gD proteins could efficiently induce mucosal immune responses against this disease (Wang J et al . 2019 ), and the efficient protection provided by a gD-based subunit vaccine against PRV variant infection in pig models was also confirmed recently (Zhang et al . 2020 ).…”

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

“…A study conducted by Zhang et al (2016) revealed that the supplementation of broiler diets with Lactococcus garvieae B301 increased the body weight and exerted a positive effect on the serum levels of immune globulins. In addition, Wang et al (2019) showed that recombinant Bacillus subtilis induces a mucosal SIgA response to pseudorabies and regulates the CD3 + CD4 + T cell proliferative response by IL-10. Another study showed that a mixture of two Clostridium strains significantly reduces the Th17/Th1 balance (Lopez et al, 2016), and infection with Clostridium perfringens or Clostridium difficile induces a pro-inflammatory response related to Th17 cells (Yacyshyn et al, 2014;Yu et al, 2017).…”

Nasal Immunization with the C-Terminal Domain of Bcla3 Induced Specific IgG Production and Attenuated Disease Symptoms in Mice Infected with Clostridioides difficile Spores

“…Due to its safety and robustness B. subtilis spores have been widely used as mucosal vaccine vehicles [ 41 , 42 , 43 ]. Recombinant B. subtilis spores administered by the nasal route have been shown able to expose the antigen to mucosal-associated lymphoid tissue (MALT) and therefore prompt a strong immune response [ 44 , 45 , 46 ]. Plus, it is shown that antigens are more protected from enzymatic lysis and have increased stability when displayed into B. subtilis spore surface than free antigen [ 26 , 47 ].…”