Design Of Oral Vaccine For Staphylococcus Aureus Based On Lactobacillus Reuteri As Delivery Vector

Staphylococcus aureus(S.aureus),a gram-positive bacterium,is one of the most common pathogens of hospital and community-related infections,which can cause many diseases such as skin,soft tissue and blood infections.The overuse of antibiotics further exacerbates the emergence of drug-resistant strains,complicating treatment of S.aureus infections,so there is an urgent need to find effective non-antibiotic therapies to solve this problem.S.aureus can infect the body through mucosal membrane,and its mucosal vaccine may be a very potential prevention method,but there are few relevant studies at present.Mucosal vaccine in the form of live vector has become one of the hot spots in the research of mucosal vaccine due to its effective protection and low cost.Lactic acid bacteria(LAB)is Generally regarded as safe(GRAS)probiotics,widely used in poultry husbandry,medicine,food and other industries.LAB shows great potential as a carrier of mucosal vaccine due to its safety and ability to regulate the body’s immune system.In this study,we chose S.aureus surface protein(Isd B)as antigen,with Lactobacillus reuteri WXD171 as the delivery carrier.Recombinant L.reuteri WXD171(PNZ8148-Isd B)was successfully constructed,and Western blot analysis showed that the recombinant L.reuteri could successfully express Isd B antigen.Compared with the wild strain,the recombinant strain had no significant differences in physiological and biochemical characteristics,acid tolerance and bile salt tolerance,and the exogenous plasmid could be inherited stably.Recombinant L.reuteri WXD171(PNZ8148-Isd B)was orally immunized in mice to investigate the immune protective effect of recombinant L.reuteri WXD171(PNZ8148-Isd B)in the model of pneumonia,skin infection and bacteremia caused by S.aureus.The results showed that oral immunization of recombinant L.reuteri WXD171(PNZ8148-Isd B)could significantly improve the survival rate of mice,reduce the amount of S.aureus colonization in the infected site,relieve inflammation and stimulate the body to produce specific antibodies Ig G and SIg A,which had a good protective effect in the mouse infection model caused by S.aureus.In conclusion,we constructed an oral S.aureus vaccine WXD171(PNZ8148-Isd B)based on L.reuteri as the delivery carrier,and verified the immune protective effect of the recombinant strain against S.aureus infection in a variety of models,providing new ideas and experimental data for the design and development of the oral S.aureus vaccine.