Proteome array of antibody responses to Chlamydia trachomatis infection in nonhuman primates

Abstract

Aims

Nonhuman primates have been used to investigate pathogenic mechanisms and evaluate immune responses following Chlamydia trachomatis inoculation. This study aimed to systemically profile antibody responses to C. trachomatis infection in nonhuman primates.

Materials and methods

Sera were obtained from 4 pig-tailed and 8 long-tailed macaques which were intravaginally or ocularly infected with live C. trachomatis organisms, and analyzed by C. trachomatis proteome array of antigens.

Key findings

The sera from 12 macaques recognized total 172 C. trachomatis antigens. While 84 antigens were recognized by pig-tailed macaques intravaginally infected with serovar D strain, 125 antigens were recognized by long-tailed macaques ocularly infected with serovar A, and 37 antigens were recognized by both. Ocular inoculation with virulent A2497 strain induced antibodies to more antigens. Among the antigens uniquely recognized by A2497 strain infected macaques, outer membrane complex B antigen (OmcB) induced robust antibody response. Although macaques infected by less virulent A/HAR-13 strain failed to develop antibodies to OmcB, reinfection by A2497 strain induced high levels of antibodies to OmcB.

Significance

Proteome array has revealed a correlation of chlamydial infection invasiveness with chlamydial antigen immunogenicity, and identified antibody responses to OmcB potentially as biomarkers for invasive infection with C. trachomatis.

Introduction

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects human in different tissue sites to cause different diseases. While ocular infection with C. trachomatis leads to blinding trachoma, C. trachomatis is a leading cause of sexually transmitted bacterial infections in the urogenital tract [1]. Because C. trachomatis infection is usually asymptomatic, many infected individuals are unaware of the acute infection and become vulnerable to repeated or persistent infection, leading to long-term consequences such as infertility [2,3]. Although excessive tissue fibrosis is thought to be the major pathological basis of both ocular and upper genital tract diseases caused by C. trachomatis, the precise mechanisms by which C. trachomatis induces pathological fibrosis remain unknown. The main serovars of C. trachomatis responsible for trachoma are A, B, and C, whereas serovars D to L3 mainly cause urogenital tract infection.

Despite the significant human health burden caused by C. trachomatis infections, there is no licensed vaccine for preventing chlamydial infections. Human trachoma vaccine trials in the 1950–70s, which was based on inactivated whole chlamydial organisms, had largely failed due to limited protective immunity induced by the vaccination and vaccination-exacerbated pathology [4,5]. The failure of the whole organism-based vaccine suggested the promise of a subunit vaccine approach. To develop an effective and safe subunit vaccine, intensive efforts have been made to identify protective and pathogenic determinants of C. trachomatis [[6], [7], [8]]. We have previously developed a glutathione-s-transferase (GST) fusion protein-based proteome array for C. trachomatis [9], which has led us to discover novel chlamydial antigens in both mice [10] and humans [11]. However, systemic evaluation of antibody responses to C. trachomatis infection in non-human primates has not been reported.

Nonhuman primates are susceptible to C. trachomatis infection in both ocular and urogenital tissues, making them ideal models for investigating chlamydial pathogenesis and immunology. Ocular infection with more invasive ocular serovars induced more severe pathology in the monkey eyes that mimics the pathology in human [12] while an attenuated plasmid-free ocular strain induced protective immunity against subsequent challenge infection with a variant strain [13]. However, inoculation with a genital strain into the nonhuman primate genital tracts was less successful in inducing upper genital tract pathology that is similar to what was observed in humans [14]. Thus, although nonhuman primates can be used for modeling both ocular and genital tract infection, the ocular infection model is more robust.

In this study, we compared the profiles of antibody responses between macaques ocularly infected and those genitally infected with C. trachomatis. In addition, we compared antibody responses in macaques ocularly infected with C. trachomatis strains of different virulence. Our results revealed a correlation of chlamydial infection invasiveness with the induction of antibody responses.