Identification of Antigens Via Protein Microarray and Assessment of Expression Library Immunization Against Cytauxzoonosis

Overview

Journal Clin Proteomics

Publisher Biomed Central

Date 2019 Jan 9

PMID 30618510

Citations 7

Authors

Megan E Schreeg

Henry S Marr

Jaime L Tarigo

Meredith K Sherrill

Hilton K Outi

Elizabeth H Scholl

David M Bird

Adam Vigil

Chris Hung

Rie Nakajima

Li Liang

Angela Trieu

Denise L Doolan

Jennifer E Thomas

Michael G Levy

Mason V Reichard

Philip L Felgner

Leah A Cohn

Adam J Birkenheuer

Affiliations

Soon will be listed here.

Abstract

Background: Cytauxzoonosis is a disease of felids in North America caused by the tick-transmitted apicomplexan parasite . Cytauxzoonosis is particularly virulent for domestic cats, but no vaccine currently exists. The parasite cannot be cultivated in vitro, presenting a significant limitation for vaccine development.

Methods: Recent sequencing of the genome has identified over 4300 putative protein-encoding genes. From this pool we constructed a protein microarray containing 673 putative proteins. This microarray was probed with sera from -infected and naïve cats to identify differentially reactive antigens which were incorporated into two expression library vaccines, one polyvalent and one monovalent. We assessed the efficacy of these vaccines to prevent of infection and/or disease in a tick-challenge model.

Results: Probing of the protein microarray resulted in identification of 30 differentially reactive antigens that were incorporated into the two expression library vaccines. However, expression library immunization failed to prevent infection or disease in cats challenged with .

Conclusions: Protein microarray facilitated high-throughput identification of novel antigens, substantially increasing the pool of characterized antigens. These antigens should be considered for development of vaccines, diagnostics, and therapeutics.

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References

Piedrafita D, Xu D, Hunter D, Harrison R, Liew F . Protective immune responses induced by vaccination with an expression genomic library of Leishmania major. J Immunol. 1999; 163(3):1467-72. View

Smooker P, Setiady Y, Rainczuk A, Spithill T . Expression library immunization protects mice against a challenge with virulent rodent malaria. Vaccine. 2000; 18(23):2533-40. DOI: 10.1016/s0264-410x(00)00018-9. View

Melby P, Ogden G, Flores H, Zhao W, Geldmacher C, Biediger N . Identification of vaccine candidates for experimental visceral leishmaniasis by immunization with sequential fractions of a cDNA expression library. Infect Immun. 2000; 68(10):5595-602. PMC: 101511. DOI: 10.1128/IAI.68.10.5595-5602.2000. View

Meinkoth J, Kocan A, Whitworth L, Murphy G, Fox J, Woods J . Cats surviving natural infection with Cytauxzoon felis: 18 cases (1997-1998). J Vet Intern Med. 2000; 14(5):521-5. DOI: 10.1892/0891-6640(2000)014<0521:csniwf>2.3.co;2. View

Rappuoli R . Reverse vaccinology, a genome-based approach to vaccine development. Vaccine. 2001; 19(17-19):2688-91. DOI: 10.1016/s0264-410x(00)00554-5. View

Long A, Mangalam H, Chan B, Tolleri L, Hatfield G, Baldi P . Improved statistical inference from DNA microarray data using analysis of variance and a Bayesian statistical framework. Analysis of global gene expression in Escherichia coli K12. J Biol Chem. 2001; 276(23):19937-44. DOI: 10.1074/jbc.M010192200. View

Baldi P, Long A . A Bayesian framework for the analysis of microarray expression data: regularized t -test and statistical inferences of gene changes. Bioinformatics. 2001; 17(6):509-19. DOI: 10.1093/bioinformatics/17.6.509. View

FERRIS D . A progress report on the status of a new disease of American cats: cytauxzoonosis. Comp Immunol Microbiol Infect Dis. 1979; 1(4):269-76. DOI: 10.1016/0147-9571(79)90028-6. View

Freeman G, HALTON J . Note on an exact treatment of contingency, goodness of fit and other problems of significance. Biometrika. 1951; 38(1-2):141-9. View

10.

Kreil D, Karp N, Lilley K . DNA microarray normalization methods can remove bias from differential protein expression analysis of 2D difference gel electrophoresis results. Bioinformatics. 2004; 20(13):2026-34. DOI: 10.1093/bioinformatics/bth193. View

11.

Barry M, Howell D, Andersson H, Chen J, Singh R . Expression library immunization to discover and improve vaccine antigens. Immunol Rev. 2004; 199:68-83. DOI: 10.1111/j.0105-2896.2004.00143.x. View

12.

Smooker P, Rainczuk A, Kennedy N, Spithill T . DNA vaccines and their application against parasites--promise, limitations and potential solutions. Biotechnol Annu Rev. 2004; 10:189-236. DOI: 10.1016/S1387-2656(04)10007-0. View

13.

Davies D, Liang X, Hernandez J, Randall A, Hirst S, Mu Y . Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci U S A. 2005; 102(3):547-52. PMC: 545576. DOI: 10.1073/pnas.0408782102. View

14.

Bondy Jr P, Cohn L, Tyler J, Marsh A . Polymerase chain reaction detection of Cytauxzoon felis from field-collected ticks and sequence analysis of the small subunit and internal transcribed spacer 1 region of the ribosomal RNA gene. J Parasitol. 2005; 91(2):458-61. DOI: 10.1645/GE-374R. View

15.

Talaat A, Stemke-Hale K . Expression library immunization: a road map for discovery of vaccines against infectious diseases. Infect Immun. 2005; 73(11):7089-98. PMC: 1273844. DOI: 10.1128/IAI.73.11.7089-7098.2005. View

16.

Birkenheuer A, Marr H, Alleman A, Levy M, Breitschwerdt E . Development and evaluation of a PCR assay for the detection of Cytauxzoon felis DNA in feline blood samples. Vet Parasitol. 2006; 137(1-2):144-9. DOI: 10.1016/j.vetpar.2005.12.007. View

17.

Birkenheuer A, Le J, Valenzisi A, Tucker M, Levy M, Breitschwerdt E . Cytauxzoon felis infection in cats in the mid-Atlantic states: 34 cases (1998-2004). J Am Vet Med Assoc. 2006; 228(4):568-71. DOI: 10.2460/javma.228.4.568. View

18.

Jackson C, Fisher T . Fatal cytauxzoonosis in a Kentucky cat (Felis domesticus). Vet Parasitol. 2006; 139(1-3):192-5. DOI: 10.1016/j.vetpar.2006.02.039. View

19.

Sundaresh S, Doolan D, Hirst S, Mu Y, Unal B, Davies D . Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques. Bioinformatics. 2006; 22(14):1760-6. DOI: 10.1093/bioinformatics/btl162. View

20.

Haber M, Tucker M, Marr H, Levy J, Burgess J, Lappin M . The detection of Cytauxzoon felis in apparently healthy free-roaming cats in the USA. Vet Parasitol. 2007; 146(3-4):316-20. DOI: 10.1016/j.vetpar.2007.02.029. View