Monoclonal immunoglobulin A antibody to the major outer membrane protein of the Chlamydia trachomatis mouse pneumonitis biovar protects mice against a chlamydial genital challenge.
In order to analyze the protective role that IgA may play in a chlamydial infection two IgA monoclonal antibodies (mAb), MoPn 4-2 and MoPn 13-2, were raised against the major outer membrane protein (MOMP) of the Chlamydia trachomatis mouse pneumonitis (MoPn) biovar. mAb MoPn 4-2 was found to be serovar specific while mAb MoPn 13-2 was species specific. mAb MoPn 4-2 recognized a surface exposed conformational epitope as shown by its ability to bind to native EBs and nonreduced MOMP while failing to bind to heat and trypsin treated EBs, to reduced MOMP and to synthetic MOMP peptides. In contrast, mAb MoPn 13-2 recognized a nonconformational epitope since it was able to bind treated EBs, to reduced MOMP and to the synthetic peptide MTTWNPTISGSGI located in variable domain 4 of the MOMP. Both mAbs agglutinated intact EBs and had in vitro neutralizing activity. However, mAb MoPn 4-2 had a 20-fold higher in vitro neutralizing ability when compared to mAb MoPn 13-2 (50% neutralization at 5 micrograms ml-1 vs 100 micrograms ml-1). In an in vitro in vivo infectivity assay, mAb MoPn 4-2 protected mice against infertility when C. trachomatis MoPn elementary bodies were preincubated with the mAb before inoculation. In addition, passive transfer of mAb MoPn 4-2 resulted in significant protection as measured by a decrease in the number of mice infected, and in the intensity and duration of vaginal shedding. These results support previous findings suggesting that IgA antibodies can play a role in protection against a chlamydial infection, and further encourage work to develop vaccination strategies that elicit mucosal immunity.
Pal
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Department of Pathology, Medical Sciences, University of California, Irvine 92697-4800, USA.
Theodor
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Peterson
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de la Maza
L M
LM
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology / Q000517:prevention & control*; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D007070:Immunoglobulin A