Modeling and implications of antibody transcytosis by human genital epithelial cells during Chlamydia trachomatis infection and challenge (MUC2P.930)

Abstract

Abstract Chlamydia trachomatis (CT) is a common sexually transmitted pathogen; there is no vaccine and infection can lead to infertility and increased susceptibility to HIV acquisition. An obligate intracellular bacterium, CT is tropic for genital columnar epithelial cells, and the endocervix is the primary site of infection in women. CT infections are usually asymptomatic, endure for months, and immunity is short-lived. However, recent epidemiology studies have identified a subgroup of women who spontaneously clear infection without treatment and are protected from re-infection. We hypothesize that genital secretions from these women will aid in the identification of site-specific immune correlates and inform vaccine design. Since animal and clinical studies suggest antibodies may play a role in protection and clearance of CT, we developed novel clinical sampling techniques and an ELISA that allows normalization and quantification of local CT-specific antibody isotypes from CT-infected women, and report significantly higher levels of CT-specific IgG/A in genital secretions compared to serum. Development of a novel in vitro endocervical epithelial model that can be infected with CT now allows us to (i) determine the protective efficacy of defined (clearer v non-clearer) patient samples against CT-challenge and (ii) explore recent observations that inflammation modulates endocervical immunoglobulin receptor expression, likely influencing antibody transport in the CT-infected cervix.