Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies

PLoS One. 2015 Oct 26;10(10):e0141209. doi: 10.1371/journal.pone.0141209. eCollection 2015.

Abstract

Background: Ocular infection with Chlamydia trachomatis can cause trachoma, which is the leading cause of blindness due to infection worldwide. Despite the large-scale implementation of trachoma control programmes in the majority of countries where trachoma is endemic, there remains a need for a vaccine. Since C. trachomatis infects the conjunctival epithelium and stimulates an immune response in the associated lymphoid tissue, vaccine regimens that enhance local antibody responses could be advantageous. In experimental infections of non-human primates (NHPs), antibody specificity to C. trachomatis antigens was found to change over the course of ocular infection. The appearance of major outer membrane protein (MOMP) specific antibodies correlated with a reduction in ocular chlamydial burden, while subsequent generation of antibodies specific for PmpD and Pgp3 correlated with C. trachomatis eradication.

Methods: We used a range of heterologous prime-boost vaccinations with DNA, Adenovirus, modified vaccinia Ankara (MVA) and protein vaccines based on the major outer membrane protein (MOMP) as an antigen, and investigated the effect of vaccine route, antigen and regimen on the induction of anti-chlamydial antibodies detectable in the ocular lavage fluid of mice.

Results: Three intramuscular vaccinations with recombinant protein adjuvanted with MF59 induced significantly greater levels of anti-MOMP ocular antibodies than the other regimens tested. Intranasal delivery of vaccines induced less IgG antibody in the eye than intramuscular delivery. The inclusion of the antigens PmpD and Pgp3, singly or in combination, induced ocular antigen-specific IgG antibodies, although the anti-PmpD antibody response was consistently lower and attenuated by combination with other antigens.

Conclusions: If translatable to NHPs and/or humans, this investigation of the murine C. trachomatis specific ocular antibody response following vaccination provides a potential mouse model for the rapid and high throughput evaluation of future trachoma vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / therapeutic use
  • Chlamydia Infections / immunology
  • Chlamydia Infections / prevention & control
  • Chlamydia trachomatis / immunology*
  • Chlamydia trachomatis / pathogenicity*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Trachoma / immunology
  • Trachoma / prevention & control*

Substances

  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines

Grant support

RJS was supported by the European Community’s European 7th Framework Program ADITEC (HEALTH-F4-2011-18 280873). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.