Intranasal vaccination of mice with three doses of recombinant CPAF (rCPAF), cloned from C. trachomatis
L2 genome, expressed and purified from an Escherichia coli
expression vector system, induces a robust anti-CPAF splenic Th1 type cellular IFNγ response, and serum and vaginal antibody responses (Murthy et al., 2007
). When administered with murine recombinant interleukin-12 (IL-12) as an adjuvant, the responses are significantly elevated and also induce mucosal anti-CPAF immunoglobulin A (IgA) responses (Murthy et al., 2007
). As shown in , mice vaccinated intranasally with rCPAF+IL-12 demonstrate significantly reduced bacterial shedding as early as day 6–8 and resolve the infection by day 15 after vaginal C. muridarum
challenge, or in approximately half the time taken to resolve the infection in unimmunized mice. Vaccination with rCPAF+IL-12 also substantially protects mice from the upper genital tract pathological sequelae of the infection including prolonged inflammatory cellular infiltration, fibrosis, hydrosalpinx, oviduct and uterine horn dilatation (Murthy et al., 2007
), suggesting the preservation of reproductive health. The administration of rCPAF with an alternative Th1 adjuvant, CpG deoxynucleotides, also induces comparable immunity to that of rCPAF plus IL-12 (Cong et al., 2007
). Moreover, mucosal (intranasal) or systemic (intraperitoneal) immunization with rCPAF plus CpG induces comparable protective immunity against primary chlamydial challenge. Transgenic mice expressing human leukocyte antigen (HLA)-DR4 molecules (in place of mouse MHC II) exhibit robust protective immunity against genital chlamydial challenge following rCPAF plus IL-12 vaccination, indicating the presence of protective epitopes within CPAF that are processed and presented by human HLA molecules (Murthy et al., 2006
) and suggesting the translational value of this antigen.
Fig. 1 rCPAF+IL-12 vaccination enhances the resolution of genital chlamydial infection. Animals (10 mice/group) were treated with three doses of rCPAF+IL-12, rCPAF, IL-12, or PBS (Mock). One month following the final vaccination, mice were challenged intravaginally (more ...)
CPAF vaccination-induced protective immunity brings about comparable reductions in upper genital tract pathologies to that induced by live replicating chlamydial organisms. However, while CPAF-vaccinated mice shed high numbers of bacteria at early time-points, a primary chlamydial infection induces a high degree of resistance to re-infection in approximately 60% of animals, and the mice that get infected shed much lower numbers of bacteria with complete resolution of the infection within a week after challenge (Morrison & Caldwell, 2002
). The high degree of protective immunity against secondary challenge has been shown to be mediated by both Chlamydia
T cells and antibodies, but not CD8+
T cells (Morrison et al., 2000
). The mechanisms of chlamydial clearance induced by CPAF vaccination may differ from those induced by primary chlamydial infection, as described below, which may explain the differences in kinetics of shedding.