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Infection and Immunity, August 2008, p. 3374-3389, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00048-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Genome-Wide Proteome Array Reveals a Limited Set of Immunogens in Natural Infections of Humans and White-Footed Mice with Borrelia burgdorferi ^,

Alan G. Barbour,^1,2,3* Algimantas Jasinskas,^1,2,3, Matthew A. Kayala,^4,5, D. Huw Davies,^1,3,6 Allen C. Steere,⁷ Pierre Baldi,^4,5 and Philip L. Felgner^1,3,6

Pacific Southwest Center for Research on Emerging Infections,¹ Department of Microbiology and Molecular Genetics,² Department of Medicine,³ Department of Computer Science,⁴ Institute of Genomics and Bioinformatics, University of California Irvine, Irvine, California,⁵ ImmPORT Therapeutics Inc., Irvine, California,⁶ Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts⁷

Received 14 January 2008/ Returned for modification 25 February 2008/ Accepted 5 May 2008

Humans and other animals with Lyme borreliosis produce antibodies to a number of components of the agent Borrelia burgdorferi, but a full accounting of the immunogens during natural infections has not been achieved. Employing a protein array produced in vitro from 1,292 DNA fragments representing 80% 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, 15% of the open reading frame (ORF) products (Orfs) of B. burgdorferi 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 Peromyscus leucopus mice, a major reservoir. The high-ranking set included several B. burgdorferi 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 B. burgdorferi do not elicit antibody responses during infection and that the limited sets of immunogens are similar for two different host species.

Published ahead of print on 12 May 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: R. P. Morrison

A.J. and M.A.K. contributed equally to this study.