Abstract

Advanced animal models, such as minipigs, are needed for the development of a globally requested human Chlamydia vaccine. Previous studies have shown that vaginal inoculation of sexually mature Göttingen minipigs with Chlamydia trachomatis resulted in an infection lasting only 3–5 days.The aim of this study was to evaluate the effect of targeting the upper porcine genital tract by transcervical and transabdominal intrauterine inoculation, compared to previously performed vaginal inoculation. Furthermore, we investigated the effect of the hormonal cycle, estrus vs. diestrus, on the establishment of a C. trachomatis infection in the minipig.Targeting the upper genital tract (transcervical inoculation) resulted in a longer lasting infection (at least 7 days) compared to vaginal inoculation (3–5 days). When comparing intrauterine inoculation during estrus and diestrus, inoculation during diestrus resulted in a longer lasting infection (at least 10 days) compared to estrus (3–5 days). Furthermore, we found a significant C. trachomatis specific IFN-γ response in pigs inoculated during estrus correlating with the accelerated clearance of infection in these pigs.These findings suggest that for implementation of an optimal model of C. trachomatis in minipigs, inoculation should bypass the cervix and preferable be performed during diestrus.

Highlights

  • IntroductionMice and guinea pigs are the animal models of choice, but pigs and especially minipigs have become increasingly popular as models in preclinical research due to their high level of anatomical, physiological and immunological similarities to humans [4e6]

  • Initial studies with vaginal inoculation of sexually mature Ellegaard G€ottingen minipigs with C. trachomatis Serovar D (Ct SvD) during estrus found that an infection lasting only 3e5 days could be established [8,9] making it challenging to evaluate the efficacy of vaccine induced antibody and cell-mediated immune responses

  • Within the two IU-groups given the low dose inoculum (1*105 inclusion forming units (IFUs)) only few Chlamydia bacteria could be detected by qPCR in 1/3 minipigs on day 3 pi in the group inoculated during diestrus and in 0/3 minipigs inoculated during estrus

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Summary

Introduction

Mice and guinea pigs are the animal models of choice, but pigs and especially minipigs have become increasingly popular as models in preclinical research due to their high level of anatomical, physiological and immunological similarities to humans [4e6]. These similarities suggest that pigs have major predictive value as preclinical models of vaccine efficacy. Both conventional pigs and minipigs are found to be suitable models of genital C. trachomatis infection, but minipigs are favored due to their small size at sexual maturity and specific pathogen free (SPF) status [4,6,7]. Focus has been on establishing a longer lasting infection in the porcine female genital tract to enable better evaluation of vaccine efficacy/protection

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