Mucosal Vaccination with UV-Inactivated Chlamydia suis in Pre-Exposed Outbred Pigs Decreases Pathogen Load and Induces CD4 T-Cell Maturation into IFN-γ+ Effector Memory Cells

Abstract

<jats:p>Chlamydia trachomatis (Ct) infections are the most frequent bacterial sexually transmitted disease, and they can lead to ectopic pregnancy and infertility. Despite these detrimental long-term sequelae, a vaccine is not available. Success in preclinical animal studies is essential for vaccines to move to human clinical trials. Pigs are the natural host to Chlamydia suis (Cs)—a chlamydia species closely related to Ct, and are susceptible to Ct, making them a valuable animal model for Ct vaccine development. Before making it onto market, Ct vaccine candidates must show efficacy in a high-risk human population. The high prevalence of human Ct infection combined with the fact that natural infection does not result in sterilizing immunity, results in people at risk likely having been pre-exposed, and thus having some level of underlying non-protective immunity. Like human Ct, Cs is highly prevalent in outbred pigs. Therefore, the goal of this study was to model a trial in pre-exposed humans, and to determine the immunogenicity and efficacy of intranasal Cs vaccination in pre-exposed outbred pigs. The vaccine candidates consisted of UV-inactivated Cs particles in the presence or absence of an adjuvant (TriAdj). In this study, both groups of vaccinated pigs had a lower Cs burden compared to the non-vaccinated group; especially the TriAdj group induced the differentiation of CD4+ cells into tissue-trafficking CCR7- IFN-γ-producing effector memory T cells. These results indicate that Cs vaccination of pre-exposed pigs effectively boosts a non-protective immune response induced by natural infection; moreover, they suggest that a similar approach could be applied to human vaccine trials.</jats:p>

Characteristics of Chlamydia suis Ocular Infection in Pigs

“…This strain was isolated in the late 1960s from the faeces of an asymptomatic Austrian pig [ 40 ] and is considered the type strain [ 1 ]. C. suis S45 was successfully used in several experimental studies in pigs before [ 10 , 41 , 42 ], but never in ocular infection trials.…”

Peptide ELISA and FRET-qPCR Identified a Significantly Higher Prevalence of Chlamydia suis in Domestic Pigs Than in Feral Swine from the State of Alabama, USA

“…The C. suis species-specific peptide antigens as well as the protocol of running peptide ELISA were used as previously validated and described [ 30 , 34 ]. C. suis peptide antigens were chemically synthesized with N-terminal biotin followed by a serine-glycine-serine-glycine spacer mixture Thermo Fisher Scientific, Waltham, MA, USA).…”

Testable Candidate Immune Correlates of Protection for Porcine Reproductive and Respiratory Syndrome Virus Vaccination

“…Because quantifying IFN-γ production in T-cell phenotypes is less standardized than NA titer quantification, we will only compare IFN-γ production results from our lab in isolated peripheral blood mononuclear cells taking into account the different antigen restimulation. In a Chlamydia suis vaccination study, we observed vaccinated gilts with a significant response at approximately 0.5% of CD4 + T cells upon antigen restimulation [ 172 ]. In our two challenge studies in nursery pigs, we observed the strong CD4 + T-cell responders to be closer to 0.25% IFN-γ + upon antigen restimulation [ 67 , 129 ] with the exception of one group that responded close to 0.5% [ 129 ].…”