Pgp3 monoclonal antibody inhibits the pathogenicity of Chlamydia muridarum to the genital tract of mice.

BACKGROUND

Chlamydia trachomatis (Ct) is the leading cause of tubal inflammation in women, with a high tendency for persistent asymptomatic infections. Antibiotics are currently the primary treatment for Ct infections of the reproductive tract. However, mounting evidence indicates an increasing incidence of persistent infections and recurrence due to antibiotic treatment failure, highlighting the urgent need for novel therapeutic approaches.

METHODS

In this study, a monoclonal antibody against plasmid-encoded protein Pgp3 was prepared using hybridoma technology and its effects on the pathogenicity of Ct were investigated both in vitro and in vivo.

RESULTS

Infectivity of Chlamydia muridarum (Cm) elementary bodies (EBs) increased after incubation with His-Pgp3. When Pgp3mAb-pretreated Ct EBs or Cm-infected cell lysates were used to inoculate HeLa cells, a significantly reduced number of inclusions was observed compared with untreated controls. Cm-infected HeLa cells began to secrete Pgp3 after 6 h. Infection with Cm progeny was significantly inhibited by the addition of Pgp3mAb co-cultured during the first developmental cycle of Cm. Immunofluorescence assays revealed that Pgp3mAb could not enter the host cells. His-Pgp3 stimulated the secretion of IL-6 and IL-8 in human fallopian tube epithelial cells, while Pgp3mAb inhibited this pro-inflammatory effect of His-Pgp3. Cm-infected mice subcutaneously injected with Pgp3mAb demonstrated reduced shedding of live organisms in the lower genital tract, shorter infection cycles, reduced hydrosalpinx, and a reduced inflammatory response.

CONCLUSION

Pgp3 enhanced Cm infectivity in host cells. In vitro, Pgp3mAb inhibited Cm infection by binding to secreted Pgp3 and membrane-bound Pgp3, with a more pronounced effect on secreted Pgp3. Furthermore, Pgp3mAb inhibited the pro-inflammatory effects of Pgp3, thereby attenuating the inflammatory response. Subcutaneous administration of Pgp3mAb effectively reduced Cm-induced pathogenicity in the murine reproductive tract.