Heat denatured enzymatically inactive recombinant chlamydial protease-like activity factor induces robust protective immunity against genital chlamydial challenge.
We have shown previously that vaccination with recombinant chlamydial protease-like activity factor (rCPAF) plus interleukin-12 as an adjuvant induces robust protective immunity against primary genital Chlamydia muridarum challenge in mice. Since CPAF is a protease, we compared the effects of enzymatically active and inactive (heat denatured) rCPAF to determine whether proteolytic activity is expendable for the induction of protective immunity against chlamydial challenge. Active, but not inactive, rCPAF immunization induced high levels of anti-active CPAF antibody, whereas both induced robust splenic CPAF-specific IFN-gamma production. Vaccination with active or inactive rCPAF induced enhanced vaginal chlamydial clearance as early as day 6 with complete resolution of infection by day 18, compared to day 30 in mock-vaccinated and challenged animals. Importantly, significant and comparable reductions in oviduct pathology were observed in active and inactive rCPAF-vaccinated mice compared to mock-vaccinated animals. Thus, rCPAF induced anti-chlamydial immunity is largely independent of enzymatic activity and secondary or higher order protein conformation.
Chaganty
Bharat K R
BK
South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
Murthy
Ashlesh K
AK
Evani
Shankar J
SJ
Li
Weidang
W
Guentzel
M Neal
MN
Chambers
James P
JP
Zhong
Guangming
G
Arulanandam
Bernard P
BP
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology; D010450:Endopeptidases / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology; D006358:Hot Temperature; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D008219:Lymphogranuloma Venereum / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D011489:Protein Denaturation; D013154:Spleen / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D010450:Endopeptidases; C425923:CPA factor