Protection against an intranasal challenge by vaccines formulated with native and recombinant preparations of the Chlamydia trachomatis major outer membrane protein

Abstract

To compare the ability of a native and a recombinant preparation of the major outer membrane protein of Chlamydia trachomatis mouse pneumonitis (MoPn; Ct-nMOMP and Ct-rMOMP) to protect against an intranasal (i.n.) challenge, BALB/c mice were vaccinated by the intramuscular (i.m.) and subcutaneous (s.c.) routes using CpG-1826 and Montanide ISA 720 as adjuvants. Animals inoculated i.n. with live elementary bodies (EB) of Chlamydia served as a positive control. Negative control groups were immunized with either Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) or with minimal essential medium (MEM-0). Mice immunized with Ct-rMOMP, Ct-nMOMP and EB developed a strong immune response as shown by high levels of Chlamydia specific antibodies in serum and a strong T-cell lymphoproliferative response. Following the i.n. challenge with 10(4) inclusion forming units (IFU) of C. trachomatis, mice immunized with Ct-nMOMP or Ct-rMOMP lost significantly less weight than the negative control animals immunized with Ng-rPorB or MEM-0 (P<0.05). However, mice vaccinated with the Ct-nMOMP lost less weight than those immunized with the Ct-rMOMP (P<0.05). Mice were euthanized at 10 days following the challenge, their lungs weighed and the number of IFU of Chlamydia determined. Based on the lung weight and number of IFU recovered, significant protection was observed in the groups of mice immunized with both Ct-nMOMP and the Ct-rMOMP (P<0.05). Nevertheless, significantly better protection was achieved with the Ct-nMOMP in comparison with the Ct-rMOMP (P<0.05). In conclusion, vaccination with a preparation of the nMOMP elicited a more robust protection than immunization with rMOMP, suggesting that the conformational structure of MOMP is critical for inducing strong protection.

Figure 1. Coomassie blue stained 10% SDS-PAGE of the C. trachomatis MoPn nMOMP and rMOMP and the N. gonorrhoeae rPorB

Lane 1) MW standards; Lanes 2 and 3): not-boiled and boiled Ct-nMOMP, respectively; Lanes 4 and 5): not-boiled and boiled CT-rMOMP, respectively; Lanes 6) boiled Ng-rPorB.

Figure 2. Western blots of EB probed with sera from immunized mice

Lane 1) MW standards; Lane 2) Pooled pre-infection serum; Lane 3) Serum from mice vaccinated with Ct-nMOMP; Lane 4) Serum from mice immunized with Ct-rMOMP; 5) Serum from mice vaccinated with live Ct-MoPn; 6) Serum from mice immunized with Ng-rPorB; 7) Serum from mice immunized with MEM-0; Lane 8) EB probed with a mAb to MOMP.

Figure 3. Percentage change in total body weight following the i.n. challenge

Immunized mice were challenged i.n. with 10⁴ IFU of C. trachomatis MoPn and their body weight determined daily.