The Immune Effect Of Lactic Acid Bacteria Exopolysaccharide Adjuvant On Staphylococcus Aureus Vaccine

Staphylococcus aureus is a zoonotic pathogen,which can cause a variety of infections in humans and animals.At the same time,S.aureus is also one of the most common pathogens of bacterial food poisoning.In recent years,methicillin-resistant S.aureus is widely prevalent,at present,the infection of S.aureus is facing the severe challenge of"no medicine can be treated".Therefore,it is of great economic and public health significance to strengthen the immune prevention and treatment of S.aureus infection and to develop a safe and efficient new S.aureus vaccine.For many years,researchers all over the world have actively explored the development of S.aureus vaccine,however,there is no effective vaccine available at present.Many scholars believe that the current study of S.aureus vaccine ignores the weakening and destruction of S.aureus on the innate immune system,and further affects the function of the subsequent acquired immune system.The combination of effective vaccine preparations to stimulate a stronger immune response is a possible problem to be considered in the development of S.aureus vaccine.However,the immune response induced by existing immune adjuvants is relatively single,which greatly limits the full play of vaccine immune protection.Therefore,the development of effective and safe new immune adjuvants is an important development direction of S.aureus subunit vaccine research and development in the future.Lactic acid bacteria exopolysaccharide?LAB EPS?is an active component isolated from Lactobacillus fermentation broth.Previous laboratory studies have shown that EPS could strengthen the immune activity of macrophages and BMDCs in vitro and enhanced OVA-specific immune response Th1 and Th2 type immune responses.Therefore,on the basis of previous laboratory research,two kinds of lactic acid bacteria?EPS30 and EPS29?were selected as adjuvant combining with S.aureus3S antigen(mixed with FhuD2,Hla_H35L35L and EsxA-EsxB antigens)to immunize mice.The immune protective effects of S.aureus infection in bacteremia infection model and mastitis infection model were observed,which provides a new thought for development of the adjuvant of S.aureus vaccine.The main results of this study are as follows:1.Mice were immunized with EPS30 and EPS29 adjuvants mixed with 3S antigen(mixed with FhuD2,Hla_H35L35L and EsxA-EsxB antigens).The level of antigen-specific IgG antibody,the proliferation of T lymphocytes and the expression of cytokines of T lymphocytes were detected.The results showed that EPS29 and EPS30 could significantly increase the level of antigen-specific IgG antibody and the proliferation of T lymphocytes.At the same time,EPS29 could significantly increase the proportion of CD4+IFN-?+T cells,CD4⁺IL-4⁺T cells and CD4⁺IL-17⁺T cells in the spleen of mice.2.We evaluated the protective effect of EPS adjuvant mixed S.aureus 3S antigen(mixed with FhuD2,Hla_H35L35L and EsxA-EsxB antigens)on the mouse model of the bacteremia infection by observing the survival rate of each immunized groups after infection with S.aureus,body weight,bacterial colonization and the degree of pathological changes of mice.The results showed that compared with immunization with S.aureus 3S antigen alone,EPS29 adjuvant could effectively improve the survival rate of mice infected with S.aureus,significantly reduce the colonization of S.aureus in various organs of mice,and reduce the degree of the pathological changes of various organs of mice.3.We evaluated the protective effect of EPS adjuvant mixed S.aureus 3S antigen(mixed with FhuD2,Hla_H35L35L and EsxA-EsxB antigens)on the mouse model of mastitis infection by observing the level of antigen-specific IgG antibody,the clinical symptoms of mastitis in mice,the amount of bacteria colonized in breast tissue,the degree of pathological changes and the expression of inflammatory factors IL-6,TNF-?and IL-1?.The results showed that EPS29,as an immune adjuvant,combined with 3S antigen,could significantly increase the level of antigen-specific IgG antibody.Comparing with the control group,the EPS29 adjuvant could significantly reduce the colonization of bacteria in the mammary glands of mice and Alleviate the degree of the pathological changes of the mammary gland in mice,and reduce the contents of IL-6 and TNF-?in the mammary gland.The results demonstrated that Lactic Acid bacteria adjuvant EPS29 combined with S.aureus 3S antigen can effectively protect mice from systemic and breast infections of S.aureus.Which provides experimental basis and theoretical guidance for the design of effective new adjuvant for S.aureus vaccine.