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

Abstract

Mice deficient in B-cells (μmT mice) were used to evaluate the role of antibody in enhanced chlamydial clearance and reduction of pathology afforded by vaccination with recombinant chlamydial protease-like activity factor (rCPAF). Enhanced, but comparable, chlamydial clearance was observed in μmT and wild type (WT) mice after rCPAF+CpG vaccination. Chlamydia-induced pathology was present in mock-immunized animals, but at significantly greater levels in μmT than WT mice, whereas vaccinated μmT and WT mice exhibited similar reductions in pathology. Thus, antibodies may play a role in protection against chlamydial pathology after primary infection, but were largely dispensable in rCPAF+CpG induced chlamydial clearance and reduction in pathology.

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…However, even though anti-Chlamydia antibodies are able to neutralize infection in vitro (100,101), growing evidence shows that B cells may not be important for initial chlamydial infection but, instead, play an important role in the secondary memory response (102,103). Several possible mechanisms by which B cells modulate immunity during reinfection include antibody-mediated neutralization and opsonization (100) and antibody-dependent cellular cytotoxicity (ADCC) (a mechanism of cell-mediated immune defense whereby cells that have antibodies attached to their surfaces are targeted for lysis) (104).…”

CD4+T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity toChlamydia muridarumGenital Infection

“…Subunit antigen vaccines represent the bulk of vaccine studies, and vaccines based on combinations of a number of chlamydial antigens, adjuvants, and delivery systems have had various degrees of success in preventing infection (8,22,62). Chlamydial antigens, including secreted proteins, such as chlamydial protease-like activity factor (CPAF) (16,33,(43)(44)(45)(46), and membrane associated proteins, such as PorB (26,30) and IncA (33), have also been used in subunit vaccines; however, the vast majority of studies have focused on the major outer membrane protein (MOMP), an immunodominant antigen in both human and animal studies (22,62). Novel delivery systems, including Vibrio cholerae ghosts and cationic liposomes, have been introduced into chlamydial vaccine research, and while initial studies have shown incomplete protection, these systems may have the potential to elicit protective responses against chlamydial genital infection when used in conjunction with appropriate antigens (2,19,20,23).…”

Tubal Damage, Infertility and Tubal Ectopic Pregnancy: Chlamydia trachomatis and Other Microbial Aetiologies

“…Seminal fluid is also reportedly a mechanism of microbial transfer to the female upper genital tract. Furthermore, some microorganisms have the propensity to attach to the surface of spermatozoa, whilst others are obligate intracellular parasites within the spermatozoa C. trachomatis, N. gonorrhoeae, Mycoplasma spp., Ureaplasma spp., and E. coli have all been shown to adhere to the surface of spermatozoa or form intracellular inclusions within the spermatozoa (Friberg et al, 1987;Hickey et al, 2009;James-Holmquest et al, 1974;Murthy et al, 2009;Sanchez et al, 1989;Wolner-Hanssen & Mardh 1984). Further, female partners of infected men with spermatozoa in their ejaculate had a significantly higher incidence of upper genital tract infection compared to infected men who have been vasectomised (Toth et al, 1984).…”

“…These have recently been reviewed by several groups (Cochrane et al, 2010;Farris & Morrison 2011;Hafner 2007;Hafner & McNeilly 2008;Lyons et al, 2006;Miyairi et al, 2010;Rank & Whittum-Hudson 2010). These animal models have proved invaluable in providing knowledge of many novel candidate antigens for a vaccine (Barker et al, 2008;McNeilly et al, 2007;Murthy AK et al, 2011;Murthy et al, 2009) as well as novel delivery vehicles (Xu et al, 2011) and delivery routes such as oral and transcutaneous immunization for protection of genital infections (Hickey et al, 2010;Hickey et al, 2009) and have investigated a myriad of potential adjuvants (reviewed in Cochrane et al, 2010;Farris and Morrison, 2011; and immune responses elicited following animal immunization trials (Cunningham et al, 2011;McNeilly et al, 2007;Patton et al, 1983). For example it has recently been reported that a Vibrio cholerae ghost (VCG) multisubunit chlamydial vaccine delivered to mice by the intramuscular route stimulated immune memory in these animals (Eko et al, 2011).…”

“…The fact that CTD43 has been shown to reduce (1) chlamydial infectivity in the murine model and (2) to prime a CD4+Th1 response in over 60% of patients infected with genital serovars of C. trachomatis, means that this antigen could be a promising vaccine candidate for chlamydial genital tract infections. A third candidate antigen showing great promise particularly for prevention of infertility resulting from repeated infections with C. trachomatis is the recombinant chlamydial protease-like activity factor (rCPAF) (Murthy et al, 2011).This antigen has been reviewed as a potential vaccine candidate (Murthy et al, 2009) and has successfully induced a combination of neutralising antibodies and cell-mediated responses against genital chlamydial challenge in a murine model of genital chlamydial infection (Li et al, 2010). More recent studies have reported that mice vaccinated intranasally with rCPAF and the adjuvant CpG were significantly protected against infertility as seen by a reduction in hydrosaplinx in rCPAF+CpG vaccinated mice following a primary genital challenge with C. muridarum (Murthy et al,, 2011).…”