Antibodies to Variable Domain 4 Linear Epitopes of the Major Outer Membrane Protein Are Not Associated with Chlamydia Resolution or Reinfection in Women.

is an obligate intracellular bacterium. infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for prevention, in part due to gaps in our knowledge of -specific immune responses elicited during human infections. Previous investigations of the antibody response to have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to are not well characterized, and the impact of these antibodies on infection outcome is unknown. We recently developed a technology called deep sequence-coupled biopanning that uses bacteriophage virus-like particles to display peptides from antigens and affinity select against human serum IgG. Here, we used this technology to map -specific antibodies in groups of women with defined outcomes following infection: (i) negative upon presentation for treatment ("spontaneous resolvers"), (ii) negative at a 3-month follow-up visit after treatment ("nonreinfected"), and (iii) positive at a 3-month follow-up after treatment ("reinfected"). This analysis yielded immunodominant epitopes that had been previously described but also identified new epitopes targeted by human antibody responses to We focused on human antibody responses to the variable domain 4 serovar-conserved region of the major outer membrane protein (VD4-MOMP), a previously described immunodominant epitope. All three groups of women produced IgG to the VD4-MOMP, suggesting that detection of serum antibodies to VD4-MOMP in women with urogenital infection is not associated with protection against reinfection. infection is the most common bacterial sexually transmitted infection, and infection in women can lead to pelvic inflammatory disease and infertility. No licensed vaccine exists to prevent infection, and investigations of the natural immune response may inform the design of targeted vaccines for Our study fills a gap in knowledge regarding the epitope specificity of antibody responses that are elicited in response to infection in women. We identified several new B cell epitopes for antigens and confirmed B cell epitopes that have been identified by other methods. Our finding that women produce antibodies to the VD4-MOMP regardless of infection outcome provides insight into vaccine development, suggesting that vaccines targeting VD4-MOMP may need to elicit higher-titer antibody responses than natural infection imparts or that additional vaccine targets should be pursued in the future.