Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies

被引:17
作者
Badamchi-Zadeh, Alexander [1 ]
McKay, Paul F. [1 ]
Holland, Martin J. [2 ]
Paes, Wayne [3 ,4 ]
Brzozowski, Andrzej [4 ]
Lacey, Charles [3 ]
Follmann, Frank [5 ]
Tregoning, John S. [1 ]
Shattock, Robin J. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Virol Sect, Mucosal Infect & Immun Grp, London, England
[2] London Sch Hyg & Trop Med, London WC1, England
[3] Univ York, Hull York Med Sch, Ctr Immunol & Infect, York YO10 5DD, N Yorkshire, England
[4] Univ York, Dept Chem, York Struct Biol Lab, York YO10 5DD, N Yorkshire, England
[5] Statens Serum Inst, Dept Infect Dis Immunol, Chlamydia Vaccine Res, DK-2300 Copenhagen, Denmark
来源
PLOS ONE | 2015年 / 10卷 / 10期
关键词
OUTER-MEMBRANE PROTEIN; IMMUNE-RESPONSES; VACCINE; INFECTION; PROTECTION; VIRULENCE; ADJUVANT; ISOTYPE; CELL;
D O I
10.1371/journal.pone.0141209
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:13
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