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Employing a protein array produced in vitro from 1,292 DNA fragments representing \u223c80% of the genome, we compared the antibody reactivities of sera from patients with early or later Lyme borreliosis to the antibody reactivities of sera from controls. Overall, \u223c15% of the open reading frame (ORF) products (Orfs) of<jats:italic>B. burgdorferi<\/jats:italic>in the array detectably elicited an antibody response in humans with natural infections. Among the immunogens, 103 stood out on the basis of statistical criteria. The majority of these Orfs were also immunogenic with sera obtained from naturally infected<jats:italic>Peromyscus leucopus<\/jats:italic>mice, a major reservoir. The high-ranking set included several<jats:italic>B. burgdorferi<\/jats:italic>proteins hitherto unrecognized as immunogens, as well as several proteins that have been established as antigens. The high-ranking immunogens were more likely than nonreactive Orfs to have the following characteristics: (i) plasmid-encoded rather than chromosome-encoded proteins, (ii) a predicted lipoprotein, and (iii) a member of a paralogous family of proteins, notably the Bdr and Erp proteins. The newly discovered antigens included Orfs encoded by several ORFs of the lp36 linear plasmid, such as BBK07 and BBK19, and proteins of the flagellar apparatus, such as FliL. These results indicate that the majority of deduced proteins of<jats:italic>B. burgdorferi<\/jats:italic>do not elicit antibody responses during infection and that the limited sets of immunogens are similar for two different host species.<\/jats:p>","DOI":"10.1128\/iai.00048-08","type":"journal-article","created":{"date-parts":[[2008,5,13]],"date-time":"2008-05-13T00:45:27Z","timestamp":1210639527000},"page":"3374-3389","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":150,"title":["A Genome-Wide Proteome Array Reveals a Limited Set of Immunogens in Natural Infections of Humans and White-Footed Mice with<i>Borrelia burgdorferi<\/i>"],"prefix":"10.1128","volume":"76","author":[{"given":"Alan G.","family":"Barbour","sequence":"first","affiliation":[{"name":"Pacific Southwest Center for Research on Emerging Infections"},{"name":"Department of Microbiology and Molecular Genetics"},{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Algimantas","family":"Jasinskas","sequence":"additional","affiliation":[{"name":"Pacific Southwest Center for Research on Emerging Infections"},{"name":"Department of Microbiology and Molecular Genetics"},{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Kayala","sequence":"additional","affiliation":[{"name":"Department of Computer Science"},{"name":"Institute of Genomics and Bioinformatics, University of California Irvine, Irvine, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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