Are DNA-based vaccines useful for protection against secreted bacterial toxins? Tetanus toxin test case. 1998

K U Saikh, and J Sesno, and P Brandler, and R G Ulrich
Department of Immunology and Molecular Biology, Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA.

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.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003017 Clostridium tetani The cause of TETANUS in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin.
D003602 Cytotoxicity, Immunologic The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D005260 Female Females
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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