Protection of wild-type and severe combined immunodeficiency mice against an intranasal challenge by passive immunization with monoclonal antibodies to the Chlamydia trachomatis mouse pneumonitis major outer membrane protein

Abstract

Monoclonal antibodies (MAbs) to the Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) were characterized for their ability to neutralize the infectivity of this organism in vitro and in vivo. One of the MAbs (MoPn-23) recognizes a nonlinear epitope in the MOMP, MAb MoPn-40 binds to a linear epitope in the variable domain 1 (VD1), and MAb MoPn-32 recognizes the chlamydial lipopolysaccharide. MAb MoPn-23 neutralized 50% of the infectivity of Chlamydia, as measured in vitro by using HAK (Fc gammaIII(-)) and HeLa-229 (Fc gammaIII(+)) cells at a concentration 100 times lower than MAb MoPn-40. MAb MoPn-32 had no neutralizing ability. In comparison to the control normal mouse immunoglobulin G, passive immunization of BALB/c mice with MAb MoPn-23 resulted in a highly significant protection against an intranasal (i.n.) challenge as determined by the change in body weight, the weight of the lungs, and the yield of Chlamydia inclusion-forming units (IFU) from the lungs. Passive immunization with MAb MoPn-40 resulted in a lower degree of protection, and MAb MoPn-32 afforded no protection. MAb MoPn-23 was also tested for its ability to protect wild-type (WT) and severe combined immunodeficient (SCID) C.B-17 mice against an i.n. challenge. Protection based on total body weight, lung weight, and yield of Chlamydia IFU was as effective in SCID as in WT C.B-17 mice. In conclusion, antibodies to MOMP can protect mice against a chlamydial infection in the presence or absence of T and B cells.

FIG. 1.

Percent change in mean body weight of BALB/c mice after an i.n. challenge with C. trachomatis MoPn. The animals were passively immunized with antibodies as indicated in the figure.

FIG. 2.

Percent change in mean body weight of C.B-17 WT and SCID mice after an i.n. challenge with C. trachomatis MoPn. The mice were passively immunized with antibodies as marked in the figure.

FIG. 3.

Western blots of purified C. trachomatis MoPn MOMP reacted with various MAbs. Lane 1, EZ-run prestained recombinant protein ladder (Fisher Scientific; Pittsburg, PA). Sera were collected the day of the challenge from BALB/c mice passively immunized with the antibodies NL-IgG (lane 2), MoPn-40 (lane 3), MoPn-23 (lane 4), and MoPn-32 (lane 5). Sera were also collected on day 10 after challenge from BALB/c mice passively immunized with NL-IgG (lane 6), MoPn-40 (lane 7), MoPn-23 (lane 8), and MoPn-32 (lane 9). Sera were collected before passive immunization from SCID mice (lane 10) and C.B-17 mice (lane 11). Sera were collected at day 10 after challenge from SCID C.B-17 mice passively immunized with MoPn-23 (lane 12) and SCID C.B-17 mice immunized with NL-IgG (lane 13). Sera were collected at day 10 after challenge from WT C.B-17 mice passively immunized with MoPn-23 (lane 14) and WT C.B-17 mice immunized with control NL-IgG (lane 15). Lane 16, control MAb MoPn-40.