Mucosal Vaccination with UV-Inactivated <i>Chlamydia suis</i> in Pre-Exposed Outbred Pigs Decreases Pathogen Load and Induces CD4 T-Cell Maturation into IFN-γ<sup>+</sup> Effector Memory Cells
Amanda F. Amaral,
Khondaker S. Rahman,
Andrew R. Kick,
Lizette M. Cortes,
James Robertson,
Bernhard Kaltenboeck,
Volker Gerdts,
Catherine M. O’Connell,
Taylor B. Poston,
Xiaojing Zheng,
Chuwen Liu,
Sam Y. Omesi,
Toni Darville,
Tobias Käser
Affiliations
Amanda F. Amaral
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
Khondaker S. Rahman
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Andrew R. Kick
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
Lizette M. Cortes
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
James Robertson
College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
Bernhard Kaltenboeck
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
Volker Gerdts
Vaccine and Infectious Disease Organization—International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada
Catherine M. O’Connell
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Taylor B. Poston
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Xiaojing Zheng
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Chuwen Liu
Department of Biostatistics, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC 27599, USA
Sam Y. Omesi
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Toni Darville
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Tobias Käser
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USA
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.
