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Updated: May 23, 2026
Cell-Free Scaled Production and Adjuvant Addition to a Recombinant Major Outer Membrane Protein from Chlamydia muridarum for Vaccine Development
Published on: March 16, 2022
PmpG303-311, a protective vaccine epitope that elicits persistent cellular immune responses in Chlamydia
Raymond M Johnson1, Hong Yu, Micah S Kerr
1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. raymjohn@iupui.edu
Abstract:
Urogenital Chlamydia serovars replicating in reproductive epithelium pose a unique challenge to host immunity and vaccine development. Previous studies have shown that CD4 T cells are necessary and sufficient to clear primary Chlamydia muridarum genital tract infections in the mouse model, making a protective CD4 T cell response a logical endpoint for vaccine development. Our previous proteomics studies identified 13 candidate Chlamydia proteins for subunit vaccines. Of those, PmpG-1 is the most promising vaccine candidate. To further that work, we derived a PmpG(303-311)-specific multifunctional Th1 T cell clone, designated PmpG1.1, from an immune C57BL/6 mouse and used it to investigate the presentation of the PmpG(303-311) epitope by infected epithelial cells. Epithelial presentation of the PmpG(303-311) epitope required bacterial replication, occurred 15 to 18 h postinfection, and was unaffected by gamma interferon (IFN-γ) pretreatment. Unlike epitopes recognized by other Chlamydia-specific CD4 T cell clones, the PmpG(303-311) epitope persisted on splenic antigen-presenting cells (APC) of mice that cleared primary genital tract infections. PmpG1.1 was activated by unmanipulated irradiated splenocytes from immune mice without addition of exogenous Chlamydia antigen, and remarkably, activation of PmpG1.1 by unmanipulated immune splenocytes was stronger 6 months postinfection than it was 3 weeks postinfection. Enhanced presentation of PmpG(303-311) epitope on splenic APC 6 months postinfection reflects some type of "consolidation" of a protective immune response. Understanding the antigen-presenting cell populations responsible for presenting PmpG(303-311) early (3 weeks) and late (6 months) postinfection will likely provide important insights into stable protective immunity against Chlamydia infections of the genital tract.
Insights
A Chlamydia vaccine candidate, PmpG-1, elicits a persistent CD4 T cell response. This immune response, involving specific epitopes, strengthens over time, suggesting a consolidated protective immunity against genital tract infections.
Area of Science:
- Immunology
- Microbial Pathogenesis
- Vaccine Development
Background:
- Urogenital Chlamydia infections present challenges for host immunity and vaccine design.
- CD4 T cells are crucial for clearing Chlamydia genital tract infections.
- PmpG-1 is a promising Chlamydia protein candidate for subunit vaccines.
Purpose of the Study:
- To investigate the presentation of the PmpG(303-311) epitope by infected epithelial cells.
- To understand the persistence and consolidation of T cell responses to Chlamydia antigens.
- To identify antigen-presenting cells involved in long-term protective immunity.
Main Methods:
- Derived a PmpG(303-311)-specific CD4 T cell clone (PmpG1.1).
- Studied epitope presentation on infected epithelial cells and splenic antigen-presenting cells (APCs).
- Assessed T cell clone activation by splenocytes from infected mice at different time points.
Main Results:
- Epithelial presentation of PmpG(303-311) required bacterial replication and occurred 15-18 h postinfection.
- The PmpG(303-311) epitope persisted on splenic APCs in mice that cleared infection.
- T cell activation by immune splenocytes was stronger 6 months postinfection than 3 weeks postinfection.
Conclusions:
- The PmpG(303-311) epitope presentation on APCs consolidates protective immunity against Chlamydia.
- Understanding APCs involved in early and late antigen presentation is key to stable immunity.
- This research provides insights into developing effective Chlamydia vaccines targeting CD4 T cell responses.
