Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies.
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.
Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, United Kingdom.
Alexander
A
Badamchi-Zadeh
Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, United Kingdom.
Paul F
PF
McKay
London School of Hygiene and Tropical Medicine, Keppel St, London, United Kingdom.
Martin J
MJ
Holland
Centre for Immunology and Infection, Hull York Medical School, University of York, York, United Kingdom; York Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
Wayne
W
Paes
York Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
Andrzej
A
Brzozowski
Centre for Immunology and Infection, Hull York Medical School, University of York, York, United Kingdom.
Charles
C
Lacey
Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Frank
F
Follmann
Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, United Kingdom.
John S
JS
Tregoning
Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, United Kingdom.
Robin J
RJ
Shattock
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology / Q000627:therapeutic use; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000472:pathogenicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D014141:Trachoma / Q000276:immunology / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines