MOMP-based DNA vaccination against Chlamydia trachomatis infection in a pig model

C

Chlamydiaceae infections in pig

Chlamydiaceae are Gram-negative obligate intracellular bacteria. They are responsible for a broad range of diseases in animals and humans. In pigs, Chlamydia suis, Chlamydia abortus, Chlamydia pecorum and Chlamydia psittaci have been isolated. Chlamydiaceae infections in pigs are associated with different pathologies such as conjunctivitis, pneumonia, pericarditis, polyarthritis, polyserositis, pseudo-membranous or necrotizing enteritis, periparturient dysgalactiae syndrome, vaginal discharge, return to oestrus, abortion, mummification, delivery of weak piglets, increased perinatal and neonatal mortality and inferior semen quality, orchitis, epididymitis and urethritis in boars. However, Chlamydiaceae are still considered as non-important pathogens because reports of porcine chlamydiosis are rare. Furthermore, Chlamydiaceae infections are often unnoticed because tests for Chlamydiaceae are not routinely performed in all veterinary diagnostic laboratories and Chlamydiaceae are often found in association with other pathogens, which are sometimes more easily to detect. However, recent studies have demonstrated that Chlamydiaceae infections in breeding sows, boars and piglets occur more often than thought and are economically important. This paper presents an overview on: the taxonomy of Chlamydiaceae occurring in pigs, diagnostic considerations, epidemiology and pathology of infections with Chlamydiaceae in pigs, public health significance and finally on prevention and treatment of Chlamydiaceae infections in pigs

Chlamydia trachomatis Vaccine Research through the Years

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium. It is the leading cause of bacterial sexual transmitted infections (STIs). World Health Organization figures estimated that over 90 million new cases of genital C. trachomatis infections occur worldwide each year. A vaccination program is considered to be the best approach to reduce the prevalence of C. trachomatis infections, as it would be much cheaper and have a greater impact on controlling C. trachomatis infections worldwide rather than a screening program or treating infections with antibiotics. Currently, there are no vaccines available which effectively protect against a C. trachomatis genital infection despite the many efforts that have been made throughout the years. In this paper, the many attempts to develop a protective vaccine against a genital C. trachomatis infection will be reviewed

Chlamydia suis, an emerging Chlamydiaceae species in pigs?

Chlamydiaceae are Gram-negative obligate intracellular bacteria that can infect a broad range of animals and humans. Chlamydial infection of livestock, companion animals, and other animals may result in conjunctivitis, enteritis, pneumonia, abortion, rhinitis or arthritis but there is also a high incidence of apparently asymptomatic infections. Pigs can become infected by Chlamydophila pecorum, Chlamydophila abortus, Chlamydophila psittaci and Chlamydia suis (Everett et al., 1999). Chlamydial infections are nearly endemic in the Belgian pig population as 96% of the examined sera reacted positive in a recombinant major outer membrane protein (MOMP) antigen-based ELISA (Vanrompay et al., 2004). The purpose of this study was to examine the current serological status of our pig herd and to identify the chlamydial species involved in infecting Belgian pigs. At present, 193 (97%) of 200 examined farms tested positive for Chlamydiaceae-specific antibodies. We tried to identify the Chlamydiaceae species using a diagnostic platform comprising of culture, a Chlamydiaceae-species specific microarray and a PCR for the detection of the Chlamydia suis tetracyclin resistant gene tet(C). Our results were in accordance with the serological results, as Chlamydiaceae, and especially C. suis was highly prevalent in slaughtered pigs, in pigs ending up in the autopsy room of the Provincial Laboratory for the Prevention of Animals Diseases and in four different farms dealing with reproductive disorders. Furthermore, we could demonstrate C. suis in the eyes, the respiratory, the intestinal and the reproductive tract of sows and in semen samples of boars. We found no other species, with the exception of one Cp. pecorum and one Cp. abortus strain. In the present study, we demonstrated emerging tet(C) positive C. suis strains among Chlamydiaceae infections in pigs. Moreover, C. suis, for which Koch’s postulates have already been fulfilled in the past, are widespread in pigs throughout the world. Research towards the development of preventive measurements like probiotics (Pollmann et al., 2005) or vaccines should be promoted. In the future, the spread of tetracyclin resistant C. suis strains, for instance through international trading of boar sperm, should be carefully monitored as this may present a treat to human health

Prevalence of Chlamydia abortus in Belgian ruminants

Chlamydia (C.) abortus enzootic abortion still remains the most common cause of reproductive failure in sheep-breeding countries all over the world. Chlamydia abortus in cattle is predominantly associated with genital tract disease and mastitis. In this study, Belgian sheep (n=958), goats (n=48) and cattle (n=1849) were examined, using the ID Screen (TM) Chlamydia abortus indirect multi-species antibody ELISA. In the sheep, the highest prevalence rate was found in Limburg (4.05%). The animals of Antwerp, Brabant and Liege tested negative. The prevalence in the remaining five regions was low (0.24% to 2.74%). Of the nine goat herds, only one herd in Luxembourg was seropositive. In cattle, the highest prevalence rate was found in Walloon Brabant (4.23%). The animals of Limburg and Namur tested negative. The prevalence rate in the remaining seven regions ranged between 0.39% and 4.02%

Chlamydia trachomatis L2c infection in a porcine model produced urogenital pathology and failed to induce protective immune responses against re-infection

The current study was designed to evaluate the pathogenesis, pathology and immune response of female genital tract infection with Chlamydia trachomatis L2c, the most recently discovered lymphogranuloma venereum strain, using a porcine model of sexually transmitted infections. Pigs were mock infected, infected once or infected and re-infected intravaginally, and samples were obtained for chlamydial culture, gross and microscopic pathology, and humoral and cell-mediated immunity. Intravaginal inoculation of pigs with this bacterium resulted in an infection that was confined to the urogenital tract, where inflammation and pathology were caused that resembled what is seen in human infection. Re-infection resulted in more severe gross pathology than primary infection, and chlamydial colonization of the urogenital tract was similar for primary infected and re- infected pigs. This indicates that primary infection failed to induce protective immune responses against re-infection. Indeed, the proliferative responses of mononuclear cells from blood and lymphoid tissues to C. trachomatis strain L2c were never statistically different among groups, suggesting that C. trachomatis-specific lymphocytes were not generated following infection or re-infection. Nevertheless, anti-chlamydial antibodies were elicited in sera and vaginal secretions after primary infection and re-infection, clearly resulting in a secondary systemic and mucosal antibody response. While primary infection did not protect against reinfection, the porcine model is relevant for evaluating immune and pathogenic responses for emerging and known C. trachomatis strains to advance drug and/or vaccine development in humans

A Probiotic Adjuvant Lactobacillus rhamnosus Enhances Specific Immune Responses after Ocular Mucosal Immunization with Chlamydial Polymorphic Membrane Protein C

Recent advances in the development of chlamydia vaccines, using live-attenuated or ultraviolet light-inactivated chlamydia, are paving the way for new possibilities to oppose the societal challenges posed by chlamydia-related diseases, such as blinding trachoma. An effective subunit vaccine would mitigate the risks associated with the use of a whole-cell vaccine. Our rationale for the design of an efficient subunit vaccine against Chlamydia trachomatis (Ct) is based on the membrane proteins involved in the initial Ct-host cell contact and on the route of immunization that mimics the natural infection process (i.e., via the ocular mucosa). The first aim of our study was to characterize the specific conjunctival and vaginal immune responses following eye drop immunization in BALB/c mice, using the N-terminal portion of the Ct serovar E polymorphic membrane protein C (N-PmpC) as the subunit vaccine antigen. Second, we aimed to examine the adjuvant properties of the probiotic Lactobacillus rhamnosus (LB) when formulated with N-PmpC. N-PmpC applied alone stimulated the production of N-PmpC-and Ct serovar B-specific antibodies in serum, tears and vaginal washes, whereas the combination with LB significantly enhanced these responses. The N-PmpC/LB combination initiated a T cell response characterized by an elevated percentage of CD25+ T cells and CD8+ effector T cells, enhanced CD4+ T-helper 1 skewing, and increased regulatory T cell responses. Together, these results show that eye drop vaccination with combined use of N-PmpC and a live probiotic LB stimulates specific cellular and humoral immune responses, not only locally in the conjunctiva but also in the vaginal mucosa, which could be a promising approach in Ct vaccine development