title: Computational modeling of TC0583 as a putative component of the Chlamydia muridarum V-type ATP synthase complex and assessment of its protective capabilities as a vaccine antigen.
abstract: Numerous Chlamydia trachomatis proteins have been identified as potential subunit vaccines, of which the major outer-membrane protein (MOMP) has, so far, proven the most efficacious. Recently, subunit A of the V-type ATP synthase (ATPase; TC0582) complex was shown to elicit partial protection against infection. Computational modeling of a neighboring gene revealed a novel subunit of the V-type ATPase (TC0583). To determine if this newly identified subunit could induce protection and/or enhance the partial protection provided by subunit A alone, challenge studies were performed using a combination of these recombinant proteins. The TC0583 subunit alone and concurrently with TC0582, was used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 VG as adjuvants. Vaccinated animals were challenged intranasally with Chlamydia muridarum and the course of the infection was followed. Mice immunized with individual antigens showed minimal alleviation of body weight reduction; however, mice immunized with TC0583 and TC0582 in combination, displayed weight loss levels close to those observed with MOMP. Importantly, immunization with a combination of recombinant subunit proteins reduced chlamydial inclusion forming units by approximately a log-fold. These protection levels support that, these highly conserved Chlamydia proteins, in combination with other antigens, may serve as potential vaccine candidates.
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.
authors.forename: Delia F
authors.initials: DF
authors.lastname: Tifrea
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave, Haworth Hall RM 8051, Lawrence, KS 66045, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Barta
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA.
authors.forename: Sukumar
authors.initials: S
authors.lastname: Pal
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave, Haworth Hall RM 8051, Lawrence, KS 66045, USA.
authors.forename: P Scott
authors.initials: PS
authors.lastname: Hefty
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA. Electronic address: Imdelama@uci.edu.
authors.forename: Luis M
authors.initials: LM
authors.lastname: de la Maza
mesh_terms: D025181:ATP Synthetase Complexes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002690:Chlamydia Infections / Q000517:prevention & control; D023502:Chlamydia muridarum / Q000201:enzymology* / Q000276:immunology*; D002479:Inclusion Bodies / Q000382:microbiology; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D021122:Protein Subunits; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D025181:ATP Synthetase Complexes
keywords: Antigens; Chlamydia trachomatis; Mouse; V-type ATP synthase; Vaccine