E-036. Monoclonal Antibodies to the C. trachomatis Major Outer Membrane Protein Can Protect Wild Type and SCID Mice against an Intranasal Challenge

S. Pal, J. Bravo, E. M. Peterson, L. M. de la Maza;
Univ. of California, Irvine, CA.

Chlamydia trachomatis infections have a worldwide distribution. A better understanding of the immunopathogenesis of these infections is required if we want to implement preventive measures. The role that the cell mediated and the humoral immune responses play in the control of chlamydial infections is still under investigation. Here we characterized the role that antibodies may play in protection. Monoclonal antibodies (mAb) to the C. trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) were characterized for their ability to neutralize in vitro and in vivo the infectivity of this organism. One of the mAb (MoPn-23) tested recognizes a non-linear epitope in the MOMP trimer while mAb MoPn-40 binds to a linear epitope in variable domain 1. In vitro mAb MoPn-23 neutralized 50% of the infectivity of Chlamydia in HeLa-229 cells at a concentration 100-times lower than mAb MoPn-40 (0.001 vs. 0.1 υg/ml). Passive immunization of BALB/c mice with MoPn-23 resulted in significant protection against an intranasal challenge with 104 C. trachomatis inclusion forming units (IFU). In comparison with mice passively immunized with normal mouse IgG used as a control, animals immunized with mAb MoPn-23 lost less body weight (-1% vs -20%), the weight of their lungs was less (0.28 vs 0.38g) and the median yield of Chlamydia IFU recovered from their lungs was lower (6.0 x 106 vs. 2.3 x 108 IFU). Passive immunization with mAb MoPn-40 resulted in significant but lower degree of protection compared with MoPn-23. mAb MoPn-23 was also tested for its ability to protect wild type CB.17 and severe combined immunodeficient (SCID) CB.17 mice against an intranasal challenge with 104 IFU of C. trachomatis MoPn. Protection with mAb MoPn-23, as determined based by body weight (-2% vs 3%), weight of the lungs (0.22 vs 0.21g) and the median yield of Chlamydia IFU from the lungs (9.7 x 106 vs 3.3 x 106), was as effective in SCID as in wild type mice. In conclusion, passive immunization with mAb to MOMP can protect mice against an intranasal challenge with C. trachomatis in the presence or absence of T and B cells.