Evaluating Potential Vaccine Antigens in both the &amp;lt;i&amp;gt;Chlamydia trachomatis&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;Chlamydia muridarum&amp;lt;/i&amp;gt; Intravaginal Mouse Challenge Models

Robin M Kaufhold,Julie M Skinner,Bob J Lucas,Jodie A Field,Melissa A Boddicker,Amy S Espeseth,Jeffrey G Smith,Joseph M Antonello,Jon H Heinrichs

doi:10.4236/wjv.2019.92004

Abstract

Identifying relevant animal challenge models adds to the complexity of human vaccine development. Murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The question arises as to whether the C. trachomatis or C. muridarum pre-clinical model is optimal. We compared C. muridarum and C. trachomatis intravaginal challenge models in a combined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. muridarum studies, mice immunized with Chlamydia elementary bodies (EB) demonstrated a significant reduction in urogenital bacterial shedding as measured by qPCR (p C. trachomatis studies. We have evaluated proposed vaccine antigens in both models and observed immunization with Chlamydia major outer membrane protein (MOMP) vaccine formulations to be protective (p C. trachomatis model, and immunization with PmpD p82 translocator domain was not protective in either model. We also observed in both models that depletion of CD4+ T-cells in MOMP-immunized mice resulted in diminished protective immunity but animals were still able to reduce the infection level. In contrast, mice immunized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from intravaginal challenge in either model. Overall, we have found the C. muridarum model to be a more robust, reliable, and reproducible model for vaccine antigen discovery.

Highlights

Chlamydia trachomatis is the most commonly reported disease in the United States and among the most prevalent sexually transmitted diseases
We found that in 100% (42/42) of the C. muridarum intravaginal challenge studies the elementary bodies (EB)-immunized mice showed a significant reduction in vaginal bacterial shedding assessed by qPCR (p < 0.05) compared to the adjuvant-control-immunized mice (Figure 2(A))
We have extensively evaluated the C. muridarum intravaginal challenge model and demonstrated that it is more reliable, robust, and reproducible compared to the C. trachomatis serovar D intravaginal challenge model

Summary

Introduction

Chlamydia trachomatis is the most commonly reported disease in the United States and among the most prevalent sexually transmitted diseases. Treatment is available but long-term damage to reproductive organs is common, as on average >70% of urogenital infections remain asymptomatic and are largely undiagnosed [4] [5] [6]. A Chlamydia trachomatis vaccine would address a major global unmet medical need. Several animal models have been developed to evaluate Chlamydia infections and potential vaccines. The most common is the mouse model in which two different species of Chlamydiae are used: Chlamydia muridarum, originally isolated from the lungs of reportedly normal albino Swiss mice [7] [8], and human-derived Chlamydia trachomatis strains. Neither mouse model completely mimics C. trachomatis infection in women

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Results

Conclusion