Role of lactadherin anti-idiotypic monoclonal antibodies Ab2β in the treatment of human rotavirus-induced diarrhea in a neonatal mouse model / 中国热带医学

ABSTRACT

@#Abstract Objective To investigate the preventive and therapeutic effects of anti-idiotypic monoclonal antibodies (Ab2β) of lactadherin on neonatal mice infected with human rotavirus (HRV), and to analyze the underlying mechanism. Methods Hybridoma technology was used to prepare Ab2β of lactadherin. One hundred and twenty 7-day-old Kunming mice were randomly divided into groups A, B, C and control, each consisting of 30 mice. Groups A, B, and C were all infected with HRV via oral gavage. Group A received no treatment, group B was orally administered lactadherin for 7 days prior to infection, and group C was orally administered lactadherin for 7 days after infection, the control group was orally administered cell culture medium that did not contain the virus. The clinical manifestations (diarrhea, body weight) at different time points after infection of the neonatal mice in each group were observed, and the content of rotavirus antigen in the feces of neonatal mice was detected by enzyme-linked immunosorbent assay (ELISA). After HRV infection for 7 days, immunohistochemical staining was used to examine the expression level of intercellular adhesion molecule-1 (ICAM-1) in mouse small intestinal tissues in each group. Results No diarrhea occurred in the control group at any time point. Groups A, B, and C showed diarrhea symptoms after HRV challenge for 1 day. The degree of diarrhea in groups B and C was lower than that in group A at 2-4 days after HRV challenge, and the difference was statistically significant (P<0.05). The HRV antigen content in the feces of the neonatal mice in groups B and C was lower than that in group A at 1-5 days after HRV challenge, and the difference was statistically significant (P<0.05). There was no significant difference in the degree of diarrhea and HRV antigen content between groups B and C at each time point (P>0.05). There was no significant difference in the body weight of the neonatal mice in each group before infection and 1 day after infection (P>0.05); the weight of neonatal mice in groups B and C was higher than that in group A at 3, 5 and 7 days after HRV challenge, and the difference was statistically significant (P<0.05), and there was no significant difference in body weight between groups B and C at each time point after HRV challenge (P>0.05). The number of ICAM-1 expressing cells in the small intestine of the three groups A, B, and C was higher than that of the control group after HRV challenge for 7 days, and the difference was statistically significant (P<0.05). The cell number and gray value of ICAM-1 expressing cells in groups B and C were lower than those in group A, and the difference was statistically significant (P<0.05). Conclusions Anti-idiotypic monoclonal antibodies (Ab2β) of lactadherin has a good preventive and therapeutic effects on human rotavirus infection in neonatal mice, and can significantly improve diarrhea symptoms and reduce HRV viral load. Its specific mechanism may be related to the inhibition of ICAM-1.