Whole genome identification of C. trachomatis immunodominant antigens after genital tract infections and effect of antibiotic treatment of pigtailed macaques

Abstract

The cervix and/or fallopian tubes of pigtailed macaques were experimentally infected with Chlamydia trachomatis. Their sera were collected at varying time points and screened for identification of immunodominant antigens using a whole-genome protein microarray. The effect of doxycycline treatment on the antibody response generated in these macaques was also investigated. Twenty-five female macaques were infected with C. trachomatis serovars D or E in the cervix and/or fallopian tubes. Bloods were collected at baseline and at various intervals after challenge. Serum samples were tested for antibodies using a C. trachomatis serovar D protein microarray. Twenty chlamydial antigens reacted with sera from at least 68% (17/25) of the macaques. In addition to some well-known chlamydial antigens, nine different proteins, not previously recognized as immunodominant, including four hypothetical proteins (CT005, CT066, CT360 and CT578), were identified. Monkeys infected in the fallopian tubes developed a more robust antibody response than animals inoculated in the cervix. Treatment with doxycycline significantly decreased Chlamydia-specific antibody levels. In summary, using protein microarray serum samples from experimentally infected pigtailed macaques were screened for immunodominant chlamydial antigens. These antigens can now be tested in animal models for their ability to protect and as markers of disease progression.

A re-evaluation of the role of B cells in protective immunity to Chlamydia infection

“…The murine model of Chlamydia genital tract infection has provided an invaluable system for immunologists to understand the host immune response to this infection and as noted above, recent data support a previously unappreciated role of B cells in preventing bacteria dissemination from the genital tract reinfection. Fortunately, with recent advances in proteomics, the screening of large numbers of antigens using serum samples from previously infected mice, non-human primates, and human patients has lead to discovery of a new array of antigen targets in Chlamydia [79–81]. Although the understanding of the role of B cells and antibody in Chlamydia infection is still in its infancy, the recent progress discussed in this review supports the idea that this population play an important role in the adaptive immune response to infection and thus may be key to the development of a novel vaccine for Chlamydia .…”

A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge

“…27,28 The possibility that treating with antibiotics can result in a decline of natural immunity has been considered as an explanation for these findings. 27,29,30 Hence, implementation of a vaccination programme has been proposed as a necessary strategy for decreasing the burden of chlamydial infections. [31][32][33][34][35][36][37][38] The induction of an immune response by a vaccine is under genetic control.…”

Survey of major histocompatibility complex class II diversity in pig-tailed macaques

“…Pig-tailed macaques ( Macaca nemestrina ) are important nonhuman primate models for infectious disease research, such as influenza, chlamydia, and tuberculosis (Gardner and Luciw 2008; Jegaskanda et al 2013; Patton et al 2014; Shen et al 2004). They are a particularly valuable species for studying HIV infection because they carry a nonfunctional TRIM5α variant that eliminates a major barrier for replication of HIV-1 in macaques (Brennan et al 2007; Liao et al 2007).…”