Abstract
Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development of a vaccine against Chlamydia is crucial. Whole organism-based vaccines have short-lived activity, serovar/subgroup-specific immunity and can cause adverse reactions in vaccinated subjects. The Chlamydia major outer membrane protein (MOMP) is a prime candidate for a subunit vaccine. MOMP contains four regions of sequence variability (variable domains, VDs) with B-cell and T-cell epitopes that elicit protective immunity. However, barriers for developing a MOMP-based vaccine include solubility, yield and refolding. We have engineered novel recombinant antigens in which the VDs are expressed into a carrier protein structurally similar to MOMP and suitable for recombinant expression at a high yield in a correctly folded and detergent-free form. Using a carrier such as the PorB porin from the human commensal organism N. lactamica, we show that PorB/VD chimeric proteins are immunogenic, antigenic and cross-reactive with MOMP. VDs are unique for each serovar but if combined in a single vaccine, a broad coverage against the major Chlamydia serovars can be ensured.
Highlights
Chlamydia trachomatis (Ct) is an obligate intracellular gram-negative organism that is the leading cause of bacterial sexually-transmitted infections and preventable blindness worldwide [1,2,3,4]
Evidence from the N. meningitidis PorB structure has suggested that L1 (Figure 1A,B, L1: Dark red) may be involved in inter-trimer contacts [66], and this loop was assigned a low priority for mutagenesis
Our approach is based on design of recombinant antigens composed of the immunogenic VD regions of major outer membrane protein (MOMP) expressed into the Neisserial PorB
Summary
Chlamydia trachomatis (Ct) is an obligate intracellular gram-negative organism that is the leading cause of bacterial sexually-transmitted infections and preventable blindness (trachoma) worldwide [1,2,3,4]. There are 15 major serovars of Ct: A, B, Ba and C are associated with trachoma; D–K are sexually-transmitted and cause genital, respiratory, gastrointestinal and ocular infections, and L1–L3 cause lymphogranuloma venereum [5,6]. The most common acute clinical manifestations of Chlamydia infections include urethritis, epididymitis in males and cervicitis in women. Since women are asymptomatic in most cases, the need for treatment is not always recognized, leading to progression into severe persistent infections with long-term sequelae such as pelvic inflammatory disease (PID), ectopic pregnancy and infertility [9,10]. Ct infection increases HIV transmission and human papilloma virus–induced
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