Chlamydial protease‐like activity factor mediated protection against C. trachomatis in guinea pigs

Abstract

We have comprehensively demonstrated using the mouse model that intranasal immunization with recombinant chlamydial protease-like activity factor (rCPAF) leads to a significant reduction in bacterial burden, genital tract pathology and preserves fertility following intravaginal genital chlamydial challenge. In the present report, we evaluated the protective efficacy of rCPAF immunization in guinea pigs, a second animal model for genital chlamydial infection. Using a vaccination strategy similar to the mouse model, we intranasally immunized female guinea pigs with rCPAF plus CpG deoxynucleotides (CpG; as an adjuvant), and challenged intravaginally with C. trachomatis serovar D (CT-D). Immunization with rCPAF/CpG significantly reduced vaginal CT-D shedding and induced resolution of infection by day 24, compared to day 33 in CpG alone treated and challenged animals. Immunization induced robust anti-rCPAF serum IgG 2 weeks following the last immunization, and was sustained at a high level 4 weeks post challenge. Upregulation of antigen specific IFN-γ gene expression was observed in rCPAF/CpG vaccinated splenocytes. Importantly, a significant reduction in inflammation in the genital tissue in rCPAF/CpG-immunized guinea pigs compared to CpG-immunized animals was observed. Taken together, this study provides evidence of the protective efficacy of rCPAF as a vaccine candidate in a second animal model of genital chlamydial infection.

The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection

“…caviae from the infected conjunctivae of young laboratory guinea pigs and defined it as the causative agent of guinea pig inclusion conjunctivitis [ 11 ]. The infection of guinea pigs with human Ct serovars D and E [ 12 ], and the usage of this model for Ct vaccination studies [ 13 ], was described in the genital, but not in the ocular, animal model. The major disadvantage of the ocular guinea pig model has been the lack of a wide range of immunological reagents/consumables, knockout animals, and easily accessible inbred guinea pig strains.…”

Intranasal immunization with recombinant chlamydial protease‐like activity factor attenuates atherosclerotic pathology following Chlamydia pneumoniae infection in mice

“…[2][3][4][21][22][23][24][25][26][27][28] We also have shown that rCPAF + IL-12 vaccination protects against C. muridaruminduced disease sequelae in the female mouse upper reproductive tract including hydrosalpinx formation and infertility. 3,4,27,28 However, these disease sequelae were not induced by C. trachomatis infection in mice or guinea pigs and therefore we have not been able to confirm the efficacy of the vaccine against the human pathogen. In this context, we noted that CPAF is a highly conserved chlamydial protein, and a strong association between C. pneumoniae and exacerbation of atherosclerosis in human individuals, and a cause-and-effect relationship in mice and rabbits has been demonstrated.…”

“…We have shown previously that immunization with rCPAF cloned from C. trachomatis serovar L2 genome, with IL-12 or CpG-ODN as adjuvant, can enhance clearance of C. muridarum and C. trachomatis infection in mice and guinea pigs, respectively 2-4, 21-28 . We also have shown that rCPAF+IL-12 vaccination protects against C. muridarum -induced disease sequelae in the female mouse upper reproductive tract including hydrosalpinx formation and infertility 3, 4, 27, 28 . However, these disease sequelae were not induced by C. trachomatis infection in mice or guinea pigs and therefore we have not been able to confirm the efficacy of the vaccine against the human pathogen.…”

“…We have provided compelling evidence previously that intranasal (i.n.) immunization with recombinant chlamydial protease-like activity factor (rCPAF) cloned from C. trachomatis L2 genome, with murine recombinant interleukin-12 (IL-12) or CpG deoxynucleotides (CpG-ODN) as adjuvant, significantly enhances clearance of chlamydial infection and reduces upper reproductive tract pathologies in the mouse as well as the guinea pig models of genital chlamydial infection 2-4 .…”

National Institute of Allergy and Infectious Diseases workshop report: “Chlamydia vaccines: The way forward”

“…The Ct-secreted serine protease or Chlamydia protease-like activity factor (CPAF) [74,75] is a dimeric complex [76,77] and an immunodominant antigen [78], which has been shown to promote Ct survival in the mouse lower genital tract [79], potentially via targeting host innate effectors [80,81]. Immunization with a recombinant CPAF alone, or in combination with other antigens, induced significant protection against infection and pathology in various mouse strains and guinea pigs [82][83][84][85]. The chlamydial major outer membrane protein (MOMP) is the serovar-typing antigen with multiple B and T cell epitopes [86][87][88] and has long been proposed as a vaccine candidate [89][90][91].…”