title: A novel candidate vaccine for cytauxzoonosis inferred from comparative apicomplexan genomics.
abstract: Cytauxzoonosis is an emerging infectious disease of domestic cats (Felis catus) caused by the apicomplexan protozoan parasite Cytauxzoon felis. The growing epidemic, with its high morbidity and mortality points to the need for a protective vaccine against cytauxzoonosis. Unfortunately, the causative agent has yet to be cultured continuously in vitro, rendering traditional vaccine development approaches beyond reach. Here we report the use of comparative genomics to computationally and experimentally interpret the C. felis genome to identify a novel candidate vaccine antigen for cytauxzoonosis. As a starting point we sequenced, assembled, and annotated the C. felis genome and the proteins it encodes. Whole genome alignment revealed considerable conserved synteny with other apicomplexans. In particular, alignments with the bovine parasite Theileria parva revealed that a C. felis gene, cf76, is syntenic to p67 (the leading vaccine candidate for bovine theileriosis), despite a lack of significant sequence similarity. Recombinant subdomains of cf76 were challenged with survivor-cat antiserum and found to be highly seroreactive. Comparison of eleven geographically diverse samples from the south-central and southeastern USA demonstrated 91-100% amino acid sequence identity across cf76, including a high level of conservation in an immunogenic 226 amino acid (24 kDa) carboxyl terminal domain. Using in situ hybridization, transcription of cf76 was documented in the schizogenous stage of parasite replication, the life stage that is believed to be the most important for development of a protective immune response. Collectively, these data point to identification of the first potential vaccine candidate antigen for cytauxzoonosis. Further, our bioinformatic approach emphasizes the use of comparative genomics as an accelerated path to developing vaccines against experimentally intractable pathogens.
authors: Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina, United States of America.
authors: Jaime L
authors: JL
authors: Tarigo
authors: Elizabeth H
authors: EH
authors: Scholl
authors: David
authors: D
authors: McK Bird
authors: Corrie C
authors: CC
authors: Brown
authors: Leah A
authors: LA
authors: Cohn
authors: Gregg A
authors: GA
authors: Dean
authors: Michael G
authors: MG
authors: Levy
authors: Denise L
authors: DL
authors: Doolan
authors: Angela
authors: A
authors: Trieu
authors: Shila K
authors: SK
authors: Nordone
authors: Philip L
authors: PL
authors: Felgner
authors: Adam
authors: A
authors: Vigil
authors: Adam J
authors: AJ
authors: Birkenheuer
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D002371:Cat Diseases / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D002415:Cats; D002417:Cattle; D017124:Conserved Sequence; D018503:Genome, Protozoan; D023281:Genomics; D007106:Immune Sera / Q000276:immunology; D016792:Piroplasmida / Q000235:genetics* / Q000276:immunology; D011529:Protozoan Infections, Animal / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D016052:Protozoan Vaccines / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D026801:Synteny; D016797:Theileria parva / Q000235:genetics / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D007106:Immune Sera; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins
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