Elsevier

Vaccine

Volume 22, Issues 31–32, 22 October 2004, Pages 4282-4286
Vaccine

Immune response to the Chlamydia trachomatis outer membrane protein PorB

https://doi.org/10.1016/j.vaccine.2004.04.035Get rights and content

Abstract

The antigenicity of the outer membrane protein PorB during exposure to Chlamydia trachomatis was evaluated in humans and its immunogenicity was tested in mice. Although natural human infection resulted in strong serological responses to the major outer membrane protein (OmpA), antibodies to PorB were low or absent. Analogous to the responses observed in humans, mice inoculated with EB or challenged with EB produced weak anti-PorB antibody responses. PorB immunization of mice previously exposed to EB elicited strong PorB antibody responses. These findings support the fact that OmpA antibodies dominate the humoral immune response during natural infections and demonstrate that immunization with PorB overcomes the lack of immune response to PorB elicited during natural infection.

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).

Section snippets

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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