Immune response to the Chlamydia trachomatis outer membrane protein PorB
Introduction
Chlamydiae are intracellular bacterial pathogens that pose major public health concerns worldwide. Chlamydia trachomatis causes a spectrum of diseases including trachoma in developing countries and is the leading bacterial cause of sexually transmitted diseases in industrialized countries. Chlamydia pneumoniae primarily causes upper respiratory tract infections and accounts for 6–10% of community-acquired pneumonia [1]. However, the microorganism also has been described as a causal agent for chronic conditions such as reactive arthritis and atherosclerosis [2], [3]. Chlamydial infections are characterized by an intense localized inflammatory response, with disease progression resulting from recurrent or persistent infections [4].
The C. trachomatis [5] and C. pneumoniae genome sequences [6] have shed new light on the array of proteins that may be useful as vaccine candidates. Among these is the outer membrane protein PorB [7]. Several features of PorB make it desirable for further evaluation as a potential immunogen. The protein is highly conserved among C. trachomatis serovars, is localized to the chlamydial outer membrane surface and is a target of neutralizing antibody responses in vitro [7], [8], a correlate to immune-mediated protection [9]. The surface-exposed antigenic determinants that contribute to the neutralizing response have recently been identified [8]. Furthermore, antibodies to the neutralizing antigenic determinants show cross-reactivity to C. pneumoniae PorB supporting its structural conservation across the species [8]. The goals of the present study were to assess the human immune response to PorB following natural C. trachomatis infection and to investigate the immune response following immunization with PorB in the context of a previous or subsequent exposure to elementary bodies (EB).
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Chlamydial strains
C. trachomatis strains D/UW-3/Cx and L2/434/Bu were grown in HeLa 229 cells and purified by Renografin (Squibb Diagnostics, Princeton, NJ) density gradient centrifugation. Infected cells were disrupted by sonication at 175 W for 25 s followed by centrifugation at 1000 × g for 10 min to remove cellular debris. EB were collected by centrifugation (12,000 × g; 30 min) and resuspended in 10 ml phosphate buffered saline (PBS). The EB were purified through a 30% Renografin column (58,000 × g; 40 min) to
Human antibody response to PorB following a natural chlamydial infection
PorB had been previously undetected in EB by standard biochemical methods probably because of the fact that PorB has a similar size and isoelectric point as the quantitatively predominant OmpA [7]. As a result, the natural human antibody response to PorB is unknown. If PorB is an important chlamydial antigen, a pertinent question is the nature of the antibody response to PorB following natural human chlamydial infection. IgG antibody levels to PorB in serum samples from patients diagnosed as
Discussion
The use of an effective vaccine appears to be the most viable option for the long-term control of chlamydial infections [12], [13], [14]. Such a vaccine must be capable of eliciting both humoral and cellular immune responses that are required for protection against infection and elimination of existing infections. However, vaccine development for C. trachomatis remains challenging partly due to the potential pathologic effects of the host’s immune response to chlamydiae [4], [15] and the
Acknowledgements
We thank Claudia Fenner for her critical review of the manuscript. Support was provided by the National Institute of Allergy and Infectious Diseases Grants AI40250 and AI42156. D.E.K. is a recipient of a National Research Service Award (AI10124) and a United Negro College Fund-Merck Graduate Research Dissertation Fellowship.
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2021, VaccineCitation Excerpt :It may be that the function of B cells in induced memory lymphocyte clusters, as in the work by Johnson et al., provide a distinct antigen-presenting role that is accessory to the importance of antibody prevention of systemic disease. Following the early trials of Nicolle, initial human vaccine trials focused on ocular inoculation of whole inactivated bacteria, primarily for the treatment of trachoma rather than genital tract infection (Fig. 4) [17,106-138]. These early trials showed some success in induction of low-level immunogenicity, providing initial evidence that vaccination to C. trachomatis was possible [111].
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2011, VaccineCitation Excerpt :On the other hand, the single subunit vaccines provide a straightforward approach to demonstrate that each of the antigens in the vaccine is individually sufficient to afford a high level of protective immunity. The chlamydial PmpD and PorB were selected as vaccine targets in this study because they are highly immunogenic antigens on the surface of elementary and reticulate bodies [20,21,35,36] and unlike MOMP, could generate both species- and genus-specific neutralizing antibodies. Also, both proteins are evolutionarily conserved and involved in chlamydial attachment to host cells [19,37], suggesting epitope conservation and the likelihood that immunity induced by PmpD and PorB may offer protection against all C. trachomatis serovars.
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2011, VaccineCitation Excerpt :Both proteins are evolutionarily conserved and involved in chlamydial attachment to host cells [17,21]. Also, PmpD and PorB are highly immunogenic and induce protective immunity in mice [22,23]. A delivery platform that would simultaneously present multiple antigens may represent a viable immunization and vaccine regimen to induce protective immunity against Chlamydia.
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