Efficacy of Pgp3 vaccination for Chlamydia urogenital tract infection depends on its native conformation

Abstract

Urogenital tract infections with Chlamydia trachomatis have frequently been detected among patients diagnosed with sexually transmitted infections, and such infections lead to inflammatory complications. Currently, no licensed chlamydial vaccine is available in clinical practice. We previously reported that immunization with recombinant C. trachomatis plasmid-encoded virulence factor Pgp3 provided cross-serovar protection against C. muridarum genital tract infection. Because Pgp3 is a homotrimer and human antisera only recognize the trimeric form of Pgp3, we compared the effects of the native conformation of Pgp3 (trimer) and heat-denatured Pgp3 (monomer) to determine whether the native conformation is dispensable for the induction of protective immunity against chlamydial vaginal challenge. Both Pgp3 trimer and monomer immunization induced corresponding specific antibody production, but only trimer-induced antibody recognized endogenous Pgp3, and trimer-immunized mouse splenocytes showed the highest IFN-γ production upon restimulation with the chlamydial elementary body or native Pgp3 in vitro. Importantly, only Pgp3 trimer-immunized mice showed shortened lower genital tract chlamydial shedding and decreased upper genital tract pathology. Thus, Pgp3-induced protective immunity against Chlamydia urogenital tract infection is highly dependent on the native conformation, which will guide the design of Pgp3-based polypeptides and multi-subunit chlamydial vaccines.

Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice

“…Persistent and subverted immune responses may inevitably contribute to the development of inflammatory sequelae such as tubal fibrosis. In addition, it is important to note that monomeric Pgp3 fails to trigger protective immunity against Chlamydia , indicating that the homotrimer conformation greatly contributes to the host immune response (Peng et al, 2022 ). Further exploration is required to test whether the Pgp3W234A mutant impacts the natural trimeric conformation of Pgp3, thus altering the induction of the immune response of hosts.…”

Protective Immunity against Chlamydia psittaci Lung Infection Induced by a DNA Plasmid Vaccine Carrying CPSIT_p7 Gene Inhibits Dissemination in BALB/c Mice

“…Pgp3 is one of the virulence factors of Chlamydia , which has good immunogenicity and is an excellent immune antigen. Good immune protection has been confirmed in animal experiments [ 17 , 22 ]. The autoimmunity of plasmid protein Pgp3 and its role in the pathogenesis of Chlamydia determine that a protein DNA vaccine can also be used as a candidate antigen for antichlamydial infection vaccine research.…”