Long-term clinical, microbiological, and immunological observations of a volunteer repeatedly infected with Chlamydia trachomatis

Hanna, Lavelle; Jawetz, Ernest; Dawson, C. R.; Thygeson, Phillips

doi:10.1128/jcm.16.5.895-900.1982

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…While it is possible the enrollees that were negative for EB-specific antibodies could be due to the use of serovars they were not currently infected with, we did observe negativity with enrollees currently infected with E. Serovar specific immunity has been proposed as a mechanism of protection against re-infection of the same serovar [ 98 , 99 ]. However, in a human trachoma infection, serovar cross-reactive antibodies were observed over time [ 100 ] and in the murine model, protection was observed after heterotypic challenge [ 101 ], suggesting serovar-cross reactive antibodies may be present and assist in protection against re-infection.…”

Section: Discussionmentioning

confidence: 79%

A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments

et al. 2017

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Chlamydia trachomatis (CT) is the leading sexually transmitted bacterial infection. The continued global burden of CT infection strongly predicates the need for a vaccine to supplement current chlamydial control programs. The correlates of protection against CT are currently unknown, but they must be carefully defined to guide vaccine design. The localized nature of chlamydial infection in columnar epithelial cells of the genital tract necessitates investigation of immunity at the site of infection. The purpose of this study was to develop a sensitive whole bacterial enzyme-linked immunosorbent assay (ELISA) to quantify and compare CT-specific IgG and IgA in sera and genital secretions from CT-infected women. To achieve this, elementary bodies (EBs) from two of the most common genital serovars (D and E) were attached to poly-L-lysine-coated microtiter plates with glutaraldehyde. EB attachment and integrity were verified by the presence of outer membrane antigens and the absence of bacterial cytoplasmic antigens. EB-specific IgG and IgA standards were developed by pooling sera with high titers of CT-specific antibodies from infected women. Serum, endocervical and vaginal secretions, and endocervical cytobrush specimens from CT-infected women were used to quantify CT-specific IgG and IgA which were then normalized to total IgG and IgA, respectively. Analyses of paired serum and genital samples revealed significantly higher proportions of EB-specific antibodies in genital secretions compared to sera. Cervical and vaginal secretions and cytobrush specimens had similar proportions of EB-specific antibodies, suggesting any one of these genital sampling techniques could be used to quantify CT-specific antibodies when appropriate normalization methodologies are implemented. Overall, these results illustrate the need to investigate genital tract CT antibody responses, and our assay provides a useful quantitative tool to assess natural immunity in defined clinical groups and CT vaccine trials.

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Section: Discussionmentioning

confidence: 79%

A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments

et al. 2017

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“…The kernel distribution of mucosal-derived IgG and IgA data ( Fig 1 ) visualized two distinct patient populations: those that significantly neutralized infection, and those that did not. Given that historic human and non-human primate trachoma studies suggest that immunity to Ct is serovar specific [ 37 , 38 ], we next determined if this differential inhibition could be due to differences in the antigen specificity of patient antibodies. Since MOMP, encoded by ompA , comprises the majority of the protein mass of the outer membrane of EBs and is established an immunodominant antigen, we hypothesized that patient antibodies would most efficiently inhibit infection by Ct strains matching that of the current infecting ompA genotype or genogroup.…”

Section: Resultsmentioning

confidence: 99%

“…Re-infection experiments by others showed that antibody responses are narrowly directed against the MOMP of the infecting serovar, which broadens over time to include cross-reactive antibodies until the infection is cleared [ 39 ]. Interestingly, antibodies against the serovar of the primary infection were recalled to a higher level during secondary infection with a different serovar, and antibody responses were directed mainly against the original infecting serovar, even after re-infection with an identical or different serovar [ 37 , 38 ]. Taken together, the results of historic and our own studies suggest that the serovar of the infecting strain can shape the humoral immune response.…”

Section: Discussionmentioning

confidence: 99%

Human genital antibody-mediated inhibition of Chlamydia trachomatis infection and evidence for ompA genotype-specific neutralization

et al. 2021

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The endocervix, the primary site of Chlamydia trachomatis (Ct) infection in women, has a unique repertoire of locally synthesized IgG and secretory IgA (SIgA) with contributions from serum IgG. Here, we assessed the ability of genital and serum-derived IgG and IgA from women with a recent positive Ct test to neutralize Ct elementary bodies (EBs) and inhibit inclusion formation in vitro in human endocervical epithelial cells. We also determined if neutralization was influenced by the major outer membrane protein (MOMP) of the infecting strain, as indicated by ompA gene sequencing and genotyping. At equivalent low concentrations of Ct EB (D/UW-3/Cx + E/UW-5/Cx)-specific antibody, genital-derived IgG and IgA and serum IgA, but not serum IgG, significantly inhibited inclusion formation, with genital IgA being most effective, followed by genital IgG, then serum IgA. The well-characterized Ct genotype D strain, D/UW-3/Cx, was neutralized by serum-derived IgG from patients infected with genotype D strains, genital IgG from patients infected with genotype D or E strains, and by genital IgA from patients infected with genotype D, E, or F strains. Additionally, inhibition of D/UW-3/Cx infection by whole serum, rather than purified immunoglobulin, was associated with levels of serum EB-specific IgG rather than the genotype of infecting strain. In contrast, a Ct genotype Ia clinical isolate, Ia/LSU-56/Cx, was neutralized by whole serum in a genotype and genogroup-specific manner, and inhibition also correlated with EB-specific IgG concentrations in serum. Taken together, these data suggest that (i) genital IgA most effectively inhibits Ct infection in vitro, (ii) human antibody-mediated inhibition of Ct infection is significantly influenced by the ompA genotype of the infecting strain, (iii) the genital antibody repertoire develops or matures differently compared to systemic antibody, and (iv) ompA genotype-specificity of inhibition of infection by whole serum can be overcome by high concentrations of Ct-specific IgG.

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Immune responses of mice after conjunctival exposure toChlamydia trachomatis serovar A

Barsoum

Hardin

Colley

1988

Med Microbiol Immunol

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CBA/J mice were inoculated in the lower conjunctival sac with live elementary bodies (EBs) of Chlamydia trachomatis serovar A. Recovery of chlamydia after exposure was done by culture of conjunctival swabs and draining lymph node (D-LN) cells in McCoy cells grown on coverslips in isolation vials. Cellular immune responsiveness was measured by lymphocyte proliferation assay of D-LN cells stimulated with irradiated EBs of serovars A, C, or L2. Humoral immunity was measured by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Chlamydia were consistently isolated from the conjunctiva and from the D-LN at 1 and 7 days after exposure respectively. Intermittent isolations were obtained from the conjunctiva up to day 4 and from the D-LN up to day 14 after a single exposure. Serovar A EB-stimulated lymphocyte proliferation was strong by 1 week after conjunctival exposure, but by 4 and 5 weeks, blastogenic responsiveness was very low. This lack of responsiveness may reflect a state of immunosuppression. Responses to serovars C and L2 EBs were consistently lower than to serovar A EBs. Serum IgG antichlamydia antibodies were not detected by ELISA until 2 weeks after exposure, peaked by 4-5 weeks, and decreased between 5 and 7 weeks after exposure. The IgM response was minimal at all times tested. There was, however, a modest increase in IgM antibodies at 3 and 5-7 weeks after exposure. Immunoblot analysis showed reactivity of mouse serum antibodies with polypeptide bands of 30, 41, and 52 kD at 3 and 4 weeks post exposure and predominantly with the 52 kD moiety at 5 weeks post exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Long-term clinical, microbiological, and immunological observations of a volunteer repeatedly infected with Chlamydia trachomatis

Cited by 7 publications

References 12 publications

A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments

A novel whole-bacterial enzyme linked-immunosorbant assay to quantify Chlamydia trachomatis specific antibodies reveals distinct differences between systemic and genital compartments

Human genital antibody-mediated inhibition of Chlamydia trachomatis infection and evidence for ompA genotype-specific neutralization

Immune responses of mice after conjunctival exposure toChlamydia trachomatis serovar A

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