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Infection and Immunity, April 2005, p. 2298-2305, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2298-2305.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

DNA Immunization with Na+-K+ATPase (Sseat-6) Induces Protective Immunity to Larval Strongyloides stercoralis in Mice

Laura A. Kerepesi,1,{dagger} Paul B. Keiser,2,{dagger} Thomas J. Nolan,3 Gerhard A. Schad,3 David Abraham,1 and Thomas B. Nutman2*

Department of Microbiology and Immunology, Thomas Jefferson University,1 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,3 Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland2

Received 23 September 2004/ Returned for modification 25 October 2004/ Accepted 26 November 2004

Strongyloides stercoralis causes chronic asymptomatic infections which can be maintained in the human host for many decades. Identification and treatment of S. stercoralis-infected individuals is required because immunosuppression can lead to fatal hyperinfection. In this study, human immunoglobulin G (IgG) that had previously been shown to transfer protective immunity to mice was used to identify potential protective antigens. Three antigens or genes from S. stercoralis larvae were identified as tropomyosin (Sstmy-1), Na+-K+ATPase (Sseat-6), and LEC-5 (Sslec-5). The genes were cloned into plasmids for DNA immunization, and mice were immunized intradermally with the three plasmids individually in combination with a plasmid containing murine granulocyte-macrophage colony-stimulating factor. Only Na+-K+ATPase induced a significant reduction in larval survival after DNA immunization. Immunization with a combination of all three plasmids, including Na+-K+ATPase, did not induce protective immunity. Serum from mice immunized with DNA encoding Na+-K+ATPase was transferred to naïve mice and resulted in partial protective immunity. Therefore, DNA immunization with Na+-K+ATPase induces protective immunity in mice, and it is the first identified vaccine candidate against infection with larval S. stercoralis.

* Corresponding author. Mailing address: Laboratory of Parasitic Diseases, National Institutes of Health, Building 4, Room B1-03, 4 Center Dr., Bethesda, MD 20892-0425. Phone: (301) 496-5398. Fax: (301) 480-3757. E-mail: tnutman{at}niaid.nih.gov.

Editor: W. A. Petri, Jr.

{dagger} L.A.K. and P.B.K. contributed equally, and both should be considered first authors.

Infection and Immunity, April 2005, p. 2298-2305, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2298-2305.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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