Effect Of Emergency Vaccine Immunization Against Leptospirosis In Nasal Mucosal Infection Model

Leptospirosis is a fatal zoonosis caused by contact between skin or a mucosal surface and contaminated soil or water.Hamsters were infected by intraperitoneal injection to establish experimental leptospirosis,which is not a natural route of infection.There are no reports of nasal mucosal infection in hamsters.Vaccines are often used to prevent leptospirosis.However,few studies have reported the therapeutic effect of a vaccine against Leptospira infection.Therefore,this study simulates the construction of a natural infection model of leptospirosis in a laboratory environment,and evaluates the emergency immunotherapy effect of leptospiral vaccine in this model and conventional intraperitoneal infection model.Firstly,the study infection of the nasal mucosa was performed to establish a model of natural infection.Both methods of infection can cause lethal models with similar symptoms in the later stages of infection,such as weight loss,blood concentration,increased neutrophils(GRAN),and decreased lymphocytes(LYM)in the blood,severe organ damage and liver function obstruction.The burden of leptospira in the organs and blood was lower in the mucosal inoculation groups at 1 day after infection.However,mucosal infection induced a higher Leptospira burden in urine than intraperitoneal infection in the late stages of infection.After nasal mucosal infection,antibody levels were higher and lasted longer.These results indicated that the route of nasal mucosal infection is a good choice for studying leptospirosis in hamsters.Under the natural conditions prone to enrichment of leptospirosis such as flooding,the therapeutic effects of emergency vaccine immunization have been rarely studied.Therefore,in the natural infection model and the conventional intraperitoneal infection model,this study evaluates the therapeutic effect and cross-protection effect of vaccine emergency immunization on leptospirosis.Based on the natural infection and intraabdominal infection models,three dose emergency vaccine immunization at 24 h,48 h and 72 h in the early stage of infection.Which had a significant therapeutic effect on leptospirosis,and increased the survival rate of hamsters to 100 % in the total lethal model.At the same time,had a therapeutic effect on multi-serotype infection.Further exploring its mechanism of action,it was found that emergency vaccine immunity can activate Toll-like receptors TLR 2 and TLR 4,while upregulating the expression of proinflammatory factors such as TNF-α and IL-1 β,and mobilizing innate immunity and adaptive immunotherapy for leptospirosis.