DNA immunization with Na+-K+ ATPase (Sseat-6) induces protective immunity to larval Strongyloides stercoralis in mice.
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 naive 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.
Kerepesi
Laura A
LA
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Keiser
Paul B
PB
Nolan
Thomas J
TJ
Schad
Gerhard A
GA
Abraham
David
D
Nutman
Thomas B
TB
D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007814:Larva / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000276:immunology*; D017171:Strongyloides stercoralis / Q000276:immunology*; D013322:Strongyloidiasis / Q000517:prevention & control; D014335:Tropomyosin / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D014335:Tropomyosin; D019444:Vaccines, DNA; D000254:Sodium-Potassium-Exchanging ATPase