Induction of protective immunity against a Chlamydia trachomatis genital infection in three genetically distinct strains of mice

Abstract

SUMMARYTo establish the feasibility of inducing a protective immune response against a chlamydial genital infection in animals with different genetic backgrounds, groups of C3H/HeN (H-2 k ), BALB/c (H-2 d ) and C57BL/6 (H-2 b ) mice, were immunized intranasally with elementary bodies (EB) of the Chlamydia trachomatis mouse pneumonitis biovar. Following the intranasal immunization strong Chlamydia-speci®c humoral and cell-mediated immune (CMI) responses were detected in the three strains of mice. Eight weeks following immunization the animals were challenged with C. trachomatis in the genital tract. Vaginal cultures showed that the three strains of mice immunized with EB were signi®cantly protected in comparison to the sham immunized animals. To determine the ability of this immunization protocol to protect against infertility six weeks after the genital challenge the animals were mated. Mice of the three strains immunized with EB showed signi®cant protection as demonstrated by the number of animals that were fertile, and the number of embryos present in their uterine horns, in comparison to the sham immunized mice.

Liposome Delivery ofChlamydia muridarumMajor Outer Membrane Protein Primes a Th1 Response That Protects against Genital Chlamydial Infection in a Mouse Model1

“…ELISpot analysis showed a significant higher number of IFN-␥-producing splenocytes in the MOMP/CAF01 group (mean Ϯ SE, 483 Ϯ 129 spots/1 ϫ 10 6 cells) than in a pool of mice treated with saline, CAF01, or alum (control pool) (P Ͻ .01), whereas the MOMP/alum-vaccinated group did not differ significantly from control mice (mean Ϯ SE, 16 Ϯ 5 spots/1 ϫ 10 6 cells) (figure 1F). In a separate experiment, intranasally infected mice were completely protected against a secondary vaginal infection with C. muridarum (data not shown), in accordance with findings of other studies [14,33]. The anti-rMOMP antibody profile and titers in these mice were found to be similar to those in an MOMP/CAF01-vaccinated group, with high anti-rMOMP IgG2b titers (average EC 50 , 3.2 log) and low anti-rMOMP IgG1 titers (average EC 50 , 0.9 log).…”

“…This response was able to protect against vaginal challenge with chlamydia (figures 2, 4, and 5) and was not due to adjuvant-induced nonspecific responses (figure 3 and table 2). Levels of IgG2b and IFN-␥ after MOMP/CAF01 vaccination reached the same magnitude found in animals after nasal challenge with C. muridarum, a protocol that has been reported elsewhere [14,33] and confirmed in our laboratory to promote complete protection against C. muridarum intravaginal challenge. CMI protection against challenge with chlamydia was clearly demonstrated by depleting the CD4 ϩ T cell subset after vaccination and before challenge with chlamydia, which resulted in an almost complete loss of protection (figure 4B).…”

Endogenous IFN-γ Production Is Induced and Required for Protective Immunity against Pulmonary Chlamydial Infection in Neonatal Mice

“…Additionally, elevated levels of serum IL-6, a cytokine associated with muscular wasting and morbidity (36), were detected during the course of the infection (days 4 -10 after challenge) in C57BL/6, but not BALB/c, mice (M. Jupelli and P. Arulanandam, unpublished observations). Such differential resolution of chlamydial infection and induction of pathology in different strains of mice have been reported by others (37)(38)(39)(40). The observed strain-specific differences in immune response were not surprising, because the relative Th1 bias in C57BL/6 mice vs a Th2 bias in BALB/c mice also has been reported (41)(42)(43).…”

Effects of RepeatedChlamydia pneumoniaeInoculations on Aortic Lipid Accumulation and Inflammatory Response in C57BL/6J Mice

“…These analyses showed that IgG1 antibodies were present only at trace levels, whereas the IgG2c antibody levels were high, especially those against the cHsp60 protein. The dominance of subtype IgG2c was expected, since the predominance of the TH1 response in chlamydial murine infection models has been shown previously (37,40). Only in group I, with six chlamydial inoculations, did the cHsp60 IgG1 antibody levels increase above the baseline at 32 weeks of age, 4 weeks after the last inoculation, suggesting that there was a weak TH2-type response as well.…”