Chlamydia trachomatis genital tract infection of antibody-deficient gene knockout mice

Abstract

The importance of antibody-mediated immunity in primary and secondary Chlamydia trachomatis genital tract infections was examined by using a definitive model of B-cell deficiency, the MT/MT gene knockout mouse. Vaginally infected B-cell-deficient MT/MT mice developed a self-limiting primary infection that was indistinguishable from infection of control C57BL/6 mice. Sera and vaginal secretions from infected mice were analyzed for anti-Chlamydia antibodies. C57BL/6 mice produced high-titered serum anti-Chlamydia immunoglobulin G2a (IgG2a), IgG2b, and IgA antibodies, and vaginal washes contained predominately anti-Chlamydia IgA. Serum and vaginal washes from infected B-cell-deficient mice were negative for anti-Chlamydia antibody. T-cell proliferation and delayed-type hypersensitivity assays were used as measures of Chlamydia-specific cell-mediated immunity and were found to be comparable for C57BL/6 and B-cell-deficient mice. Seventy days following primary infection, mice were rechallenged to assess acquired immunity. B-cell-deficient mice which lack anti-Chlamydia antibodies were more susceptible to reinfection than immunocompetent C57BL/6 mice. However, acquired immune resistance was evident in both strains of mice and characterized by decreased shedding of chlamydiae and an infection of shorter duration. Thus, this study demonstrates that cell-mediated immune responses alone were capable of resolving chlamydial infection; however, in the absence of specific antibody, mice were more susceptible to reinfection. Therefore, these data suggest that both humoral and cell-mediated immune responses were important mediators of immune protection in this model, though cell-mediated immune responses appear to play a more dominant role.

A limited role for antibody in protective immunity induced by rCPAF and CpG vaccination against primary genitalChlamydia muridarumchallenge

“…Additionally, antibody may influence the activation of CD4 1 CD25 1 regulatory T cells (Yi et al, 2008), which have been proposed to play a protective role against Chlamydia-induced pathology Johansson & Lycke, 2003;Brunham & Rey-Ladino, 2005). mmT mice also have been shown to exhibit a greater frequency of splenic T cells and phagocytes compared with WT animals (Su et al, 1997).…”

A recombinant multivalent combination vaccine protects againstChlamydiaand genital herpes

“…The VCG delivery vector together with the mouse genital infection model provided a convenient ap-proach for evaluating the immunogenicity and protective efficacy of the bivalent combination vaccine formulation comprising rVCG expressing chlamydial MOMP and HSV-2 glycoprotein D. The results obtained are encouraging, because mice immunized with the combination vaccine were prophylactically protected from genital challenge with high doses of live Chlamydia and HSV-2. An effective combination vaccine against Chlamydia and HSV-2 will most probably need to elicit effective Th1 cellmediated immune responses as well as accessory or neutralizing antibodies (Rank, 1994;Cotter, 1997;Perry et al, 1997;Su, 1997). Significant levels of Th1 responses were induced following immunization, as indicated by the production of high levels of IFN-g compared with IL-4 levels that remained unchanged up to 8 weeks postimmunization.…”

“…This is indicated by a decrease in the amount of IFN-g secreted by T cells from mice immunized with the combination vaccine; this formulation contains 50% of the antigen dose present in the single subunit vaccines. High IFN-g and low IL-4 levels are indicative of a Th1 response (Maggi, 1992;Bradley et al, 1995;Igietseme et al, 2003), which has previously been correlated with a degree of protection against both Chlamydia and HSV infections (Rank, 1994;Cotter, 1997;Perry et al, 1997;Su, 1997) (Koelle, 1998;Sin, 1999).…”

Identification and characterization of novel recombinant vaccine antigens for immunization against genitalChlamydia trachomatis

“…The use of various mouse gene-knockout strains (Cotter et al, 1997;Johansson et al, 1997;Su et al, 1997), in vivo depletion of specific lymphocyte populations, and transfer of immune lymphocyte populations to naïve mice led to the notion that C. trachomatis immunity is mediated by mucosal immunoglobulin A (IgA) antibodies, IgG molecules that transmigrate the gut epithelium, and T-helper type 1 (Th1) CD41 T cells secreting interferon-g (IFN-g) (Cain & Rank, 1995;Morrison et al, 1995;Perry et al, 1997;Igietseme & Murdin, 2000;Morrison & Morrison, 2001;Igietseme et al, 2002;Morrison & Caldwell, 2002;Barr et al, 2005;Brunham & Rey-Ladino, 2005). B-cell-deficient mice are comparable to wild-type mice in overcoming primary infection, suggesting that B cells play only a minor role in preventing an initial infection.…”