Fasciola: kinetics and quality of humoral responses to fatty acid binding protein and cathepsin l following delivery as DNA vaccines in mice.
The humoral response to DNA vaccination of mice with two important Fasciola antigens has been investigated. Both F. gigantica fatty acid binding protein (FABP) and F. hepatica cathepsin L5 (FhCatL5) were shown to be expressed in COS 7 cells and induced a humoral response when delivered as secretory constructs in mice. FABP induced an IgGl dominant response, with significant IgE, IgG2a, and IgG2b responses also present, indicating a mixed Th1/Th2 response. The total Ig response peaked at 1:24,500 and antibody titers were sustained for at least 32 weeks. In contrast, the delivery of FABP as a nonsecreted construct did not result in the induction of a measurable humoral response. FhCatL5 was delivered as a secretory construct, with secretion mediated by the native F. hepatica signal sequence, which was shown to operate in COS 7 cells. The humoral response peaked at 1:2000 at week 8 and was sustained for at least 20 weeks. Antibody isotype analysis demonstrated a Th2-like response, which was qualitatively different from that obtained for FABP with an IgE dominant response, and lower titers to IgG1 and IgG3. The results demonstrate that Fasciola antigens can be delivered as DNA vaccines, but that the quality of the response varies between antigens and is influenced by the method of vaccine delivery.
Smooker
P M
PM
Department of Biochemistry and Molecular Biology, Monash University, 3800, Australia. peter.smooker@rmit.edu.au
Kennedy
N J
NJ
Steeper
K R
KR
Christopoulos
H
H
Spithill
T W
TW
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000276:immunology*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D004797:Enzyme-Linked Immunosorbent Assay; D005209:Fasciola / Q000235:genetics / Q000276:immunology*; D005210:Fasciola hepatica / Q000235:genetics / Q000276:immunology; D005211:Fascioliasis / Q000517:prevention & control*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019444:Vaccines, DNA / Q000276:immunology*
D000909:Antibodies, Helminth; D000943:Antigens, Differentiation; D000947:Antigens, Helminth; D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019444:Vaccines, DNA; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat