{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:03:27Z","timestamp":1791158607238,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>There is currently a need for improved serological tests for the diagnosis and monitoring of Lyme disease, an infection caused by<jats:italic>Borrelia burgdorferi<\/jats:italic>. In the present study, we evaluated luciferase immunoprecipitation systems (LIPSs) for use for profiling of the antibody responses to a panel of<jats:italic>B. burgdorferi<\/jats:italic>proteins for the diagnosis of Lyme disease. Initially, serum samples from a cohort of patients and controls (<jats:italic>n<\/jats:italic>= 46) were used for training and were profiled by the use of 15 different<jats:italic>B. burgdorferi<\/jats:italic>antigen constructs. For the patient sera, the antibody responses to several<jats:italic>B. burgdorferi<\/jats:italic>antigens, including VlsE, flagellin (FlaB), BmpA, DbpA, and DbpB, indicated that the antigens had high levels of immunoreactivity. However, the best diagnostic performance was achieved with a synthetic protein, designated VOVO, consisting of a repeated antigenic peptide sequence, VlsE-OspC-VlsE-OspC, Analysis of an independent set of serum samples (<jats:italic>n<\/jats:italic>= 139) used for validation showed that the VOVO LIPS test had 98% sensitivity (95% confidence interval [CI], 93% to 100%;<jats:italic>P<\/jats:italic>&lt; 0.0001) and 100% specificity (95% CI, 94% to 100%;<jats:italic>P<\/jats:italic>&lt; 0.0001). Similarly, the C6 peptide enzyme-linked immunosorbent assay (ELISA) also had 98% sensitivity (95% CI, 93% to 100%;<jats:italic>P<\/jats:italic>&lt; 0.0001) and 98% specificity (95% CI, 90% to 100%;<jats:italic>P<\/jats:italic>&lt; 0.0001). Receiver operating characteristic analysis revealed that the rates of detection of Lyme disease by the LIPS test and the C6 ELISA were not statistically different. However, the VOVO LIPS test displayed a wide dynamic range of antibody detection spanning over 10,000-fold without the need for serum dilution. These results suggest that screening by the LIPS test with VOVO and other<jats:italic>B. burgdorferi<\/jats:italic>antigens offers an efficient quantitative approach for evaluation of the antibody responses in patients with Lyme disease.<\/jats:p>","DOI":"10.1128\/cvi.00476-09","type":"journal-article","created":{"date-parts":[[2010,4,15]],"date-time":"2010-04-15T01:54:20Z","timestamp":1271296460000},"page":"904-909","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Rapid, Simple, Quantitative, and Highly Sensitive Antibody Detection for Lyme Disease"],"prefix":"10.1128","volume":"17","author":[{"given":"Peter D.","family":"Burbelo","sequence":"first","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research"},{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra T.","family":"Issa","sequence":"additional","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research"},{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn H.","family":"Ching","sequence":"additional","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research"},{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey I.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research"},{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Iadarola","sequence":"additional","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research"},{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Marques","sequence":"additional","affiliation":[{"name":"Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research"},{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"590","volume":"44","year":"1995","unstructured":"Anonymous. 1995. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb. Mortal. Wkly. Rep.44:590-591.","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1086\/374395","volume":"187","year":"2003","unstructured":"Bacon, R. M., B. J. Biggerstaff, M. E. Schriefer, R. D. Gilmore, Jr., M. T. Philipp, A. C. Steere, G. P. Wormser, A. R. Marques, and B. J. Johnson. 2003. Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J. Infect. Dis.187:1187-1199.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/599992"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3791\/1549"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.bbrc.2006.11.140","volume":"352","year":"2007","unstructured":"Burbelo, P. D., K. H. Ching, T. L. Mattson, J. S. Light, L. R. Bishop, and J. A. Kovacs. 2007. Rapid antibody quantification and generation of whole proteome antibody response profiles using LIPS (luciferase immunoprecipitation systems). Biochem. Biophys. Res. Commun.352:889-895.","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00350-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1743-422X-6-45","volume":"6","year":"2009","unstructured":"Burbelo, P. D., A. T. Issa, K. H. Ching, M. Exner, W. L. Drew, H. J. Alter, and M. J. Iadarola. 2009. Highly quantitative serological detection of anti-cytomegalovirus (CMV) antibodies. Virol. J.6:45.","journal-title":"Virol. J."},{"key":"e_1_3_2_9_2","unstructured":"J. Infect. Dis."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00474-08"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"e438","DOI":"10.1371\/journal.pntd.0000438","volume":"3","year":"2009","unstructured":"Burbelo, P. D., H. P. Leahy, M. J. Iadarola, and T. B. Nutman. 2009. A four-antigen mixture for rapid assessment of Onchocerca volvulus infection. PLoS Negl. Trop. Dis.3:e438.","journal-title":"PLoS Negl. Trop. Dis."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1742-4690-5-96","volume":"5","year":"2008","unstructured":"Burbelo, P. D., E. Meoli, H. P. Leahy, J. Graham, K. Yao, U. Oh, J. E. Janik, R. Mahieux, F. Kashanchi, M. J. Iadarola, and S. Jacobson. 2008. Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP). Retrovirology5:96.","journal-title":"Retrovirology"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00490-08"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"4323","DOI":"10.1016\/S0021-9258(18)68928-8","volume":"263","year":"1988","unstructured":"Eliasson, M., A. Olsson, E. Palmcrantz, K. Wiberg, M. Inganas, B. Guss, M. Lindberg, and M. Uhlen. 1988. Chimeric IgG-binding receptors engineered from staphylococcal protein A and streptococcal protein G. J. Biol. Chem.263:4323-4327.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00075-07"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/infdis\/165.6.1127","volume":"165","year":"1992","unstructured":"Fikrig, E., E. D. Huguenel, R. Berland, D. W. Rahn, J. A. Hardin, and R. A. Flavell. 1992. Serologic diagnosis of Lyme disease using recombinant outer surface proteins A and B and flagellin. J. Infect. Dis.165:1127-1132.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_17_2","first-page":"615","volume":"23","year":"2004","unstructured":"Fleming, R. V., A. R. Marques, M. S. Klempner, C. H. Schmid, L. G. Dally, D. S. Martin, and M. T. Philipp. 2004. Pre-treatment and post-treatment assessment of the C(6) test in patients with persistent symptoms and a history of Lyme borreliosis. Eur. J. Clin. Microbiol. Infect. Dis.23:615-618.","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.38.7.2530-2535.2000"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00340-07"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.4049\/jimmunol.163.10.5566","volume":"163","year":"1999","unstructured":"Liang, F. T., A. L. Alvarez, Y. Gu, J. M. Nowling, R. Ramamoorthy, and M. T. Philipp. 1999. An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. J. Immunol.163:5566-5573.","journal-title":"J. Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.12.3990-3996.1999"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.34.2.237-240.1996"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.idc.2007.12.011","volume":"22","year":"2008","unstructured":"Marques, A. 2008. Chronic Lyme disease: a review. Infect. Dis. Clin. North Am.22:341-360, vii-viii.","journal-title":"Infect. Dis. Clin. North Am."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.12.3474-3479.1998"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)01146-5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nm1488","volume":"13","year":"2007","unstructured":"O'Connor, K. C., K. A. McLaughlin, P. L. De Jager, T. Chitnis, E. Bettelli, C. Xu, W. H. Robinson, S. V. Cherry, A. Bar-Or, B. Banwell, H. Fukaura, T. Fukazawa, S. Tenembaum, S. J. Wong, N. P. Tavakoli, Z. Idrissova, V. Viglietta, K. Rostasy, D. Pohl, R. C. Dale, M. Freedman, L. Steinman, G. J. Buckle, V. K. Kuchroo, D. A. Hafler, and K. W. Wucherpfennig. 2007. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat. Med.13:211-217.","journal-title":"Nat. Med."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.11.4955-4960.2003"},{"key":"e_1_3_2_28_2","first-page":"1069","volume":"12","year":"2005","unstructured":"Philipp, M. T., G. P. Wormser, A. R. Marques, S. Bittker, D. S. Martin, J. Nowakowski, and L. G. Dally. 2005. A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin. Diagn. Lab. Immunol.12:1069-1074.","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1086\/589718","volume":"198","year":"2008","unstructured":"Ramanathan, R., P. D. Burbelo, S. Groot, M. J. Iadarola, F. A. Neva, and T. B. Nutman. 2008. A luciferase immunoprecipitation systems assay enhances the sensitivity and specificity of diagnosis of Strongyloides stercoralis infection. J. Infect. Dis.198:444-451.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM200107123450207","volume":"345","year":"2001","unstructured":"Steere, A. C. 2001. Lyme disease. N. Engl. J. Med.345:115-125.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_31_2","first-page":"1","volume":"5","year":"2004","unstructured":"Wang, L. F., and M. Yu. 2004. Epitope identification and discovery using phage display libraries: applications in vaccine development and diagnostics. Curr. Drug Targets5:1-15.","journal-title":"Curr. Drug Targets"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00476-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00476-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T20:27:15Z","timestamp":1685564835000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00476-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,6]]}},"alternative-id":["10.1128\/CVI.00476-09"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00476-09","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6]]},"assertion":[{"value":"2009-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}