Leptospiral Proteins Recognized during the Humoral Immune Response to Leptospirosis in Humans

doi:10.1128/IAI.69.8.4958-4968.2001

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Infection and Immunity, August 2001, p. 4958-4968, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4958-4968.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Leptospiral Proteins Recognized during the Humoral Immune Response to Leptospirosis in Humans

Hygia Guerreiro,¹^,² Júlio Croda,¹ Brendan Flannery,³ Mary Mazel,⁴ James Matsunaga,⁴^,⁵ Mitermayer Galvão Reis,¹ Paul N. Levett,⁶ Albert I. Ko,¹^,⁷^,^* and David A. Haake⁴^,⁵

Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Brazilian Ministry of Health, 40295-001,¹ and School of Pharmacy, Federal University of Bahia, 40000 Salvador,² Brazil; School of Public Health, University of California at Berkeley, Berkeley, California 94720-7360³; Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System,⁴ and Department of Medicine, UCLA School of Medicine,⁵ Los Angeles, California 90095-1688; School of Clinical Medicine and Research, University of the West Indies, Bridgetown, Barbados⁶; and Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10021⁷

Received 23 January 2001/Returned for modification 21 March 2001/Accepted 7 May 2001

Leptospirosis is an emerging zoonosis caused by pathogenic spirochetes belonging to the genus Leptospira. An understandingof leptospiral protein expression regulation is needed to developnew immunoprotective and serodiagnostic strategies. We used thehumoral immune response during human leptospirosis as a reporterof protein antigens expressed during infection. Qualitative andquantitative immunoblot analysis was performed using sera from105 patients from Brazil and Barbados. Sera from patients withother diseases and healthy individuals were evaluated as controls.Seven proteins, p76, p62, p48, p45, p41, p37, and p32, were identifiedas targets of the humoral response during natural infection. Inboth acute and convalescent phases of illness, antibodies to lipopolysaccharidewere predominantly immunoglobulin M (IgM) while antibodies toproteins were exclusively IgG. Anti-p32 reactivity had the greatestsensitivity and specificity: positive reactions were observedin 37 and 84% of acute- and convalescent-phase sera, respectively,while only 5% of community control individuals demonstrated positivereactions. Six immunodominant antigens were expressed by all pathogenicleptospiral strains tested; only p37 was inconsistently expressed.Two-dimensional immunoblots identified four of the seven infection-associatedantigens as being previously characterized proteins: LipL32 (themajor outer membrane lipoprotein), LipL41 (a surface-exposed outermembrane lipoprotein), and heat shock proteins GroEL and DnaK.Fractionation studies demonstrated LipL32 and LipL41 reactivityin the outer membrane fraction and GroEL and DnaK in the cytoplasmicfraction, while p37 appeared to be a soluble periplasmic protein.Most of the other immunodominant proteins, including p48 and p45,were localized to the inner membrane. These findings indicatethat leptospiral proteins recognized during natural infectionare potentially useful for serodiagnosis and may serve as targetsfor vaccinedesign.

^* Corresponding author. Mailing address: Centro de Pesquisas Gonçalo Moniz; Fundação Oswaldo Cruz/MS, Rua Waldemar Falcão,121; 40295-001 Salvador, Bahia, Brazil. Phone: (55 71) 356-4320,ext. 243. Fax: (55 71) 356-2155. E-mail: aik2001{at}med.cornell.edu.

Infection and Immunity, August 2001, p. 4958-4968, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4958-4968.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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