Are DNA-based vaccines useful for protection against secreted bacterial toxins? Tetanus toxin test case.
Polypeptide and DNA vaccine alternatives to the conventional tetanus toxoid were compared. Mouse immunizations with plasmid DNA that encoded the tetanus toxin C fragment polypeptide induced consistently lower antibody responses than direct immunization with the C fragment polypeptide or toxoid, yet provided some degree of protection from a lethal toxin challenge. Cytotoxic T-cell responses dominated DNA immunizations, while specific T-cell proliferation resulted from all vaccines tested. Immune responses to the DNA vaccine exhibited a T-helper type-1 propensity, while polypeptides elicited T-helper type-2 responses. The lower antibody response to the plasmid vaccine was not due to insufficient quantity of C fragment in vivo but was likely the result of a mode of antigen presentation that was less efficient for supporting antibody production. Collectively, these results suggest that polypeptide or toxoid vaccines are preferable to plasmid-based vaccination for control of diseases caused by tetanus toxin.
Department of Immunology and Molecular Biology, Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA.
K U
KU
Saikh
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Sesno
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Brandler
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RG
Ulrich
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000235:genetics; D002460:Cell Line; D003017:Clostridium tetani / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control; D013744:Tetanus Toxin / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D013745:Tetanus Toxoid / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D010446:Peptide Fragments; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D019444:Vaccines, DNA; C040635:tetanus toxin fragment C