A recombinant 63-kDa form ofBacillus anthracisprotective antigen produced in the yeastSaccharomyces cerevisiaeprovides protection in rabbit and primate inhalational challenge models of anthrax infection
Infection byBacillus anthracisis preventable by prophylactic vaccination with several naturally derived and recombinant vaccine preparations. Existing data suggests that protection is mediated by antibodies directed against the protective antigen (PA) component of the anthrax toxin complex. PA is an...
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Published in | Vaccine Vol. 24; no. 10; p. 1501 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Kidlington
Elsevier Limited
06.03.2006
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Subjects | |
Online Access | Get full text |
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Summary: | Infection byBacillus anthracisis preventable by prophylactic vaccination with several naturally derived and recombinant vaccine preparations. Existing data suggests that protection is mediated by antibodies directed against the protective antigen (PA) component of the anthrax toxin complex. PA is an 83-kDa protein cleaved in vivo to yield a biologically active 63-kDa protein. In an effort to evaluate the potential of yeast as an expression system for the production of recombinant PA, and to determine if the yeast-purified rPA63 can protect from a lethal inhalational challenge, the sequence of the 63-kDa form of PA was codon-optimized and expressed in the yeastSaccharomyces cerevisiae. Highly purified rPA63 isolated fromSaccharomycesunder denaturing conditions demonstrated reduced biological activity in a macrophage-killing assay compared to non-denatured rPA83 purified fromEscherichia coli. Rabbits and non-human primates (NHP) immunized with rPA63 and later challenged with a lethal dose ofB. anthracisspores were generally protected from infection. These results indicate that epitopes present in the 63-kDa from of PA can protect rabbits and non-human primates from a lethal spore challenge, and further suggest that a fully functional rPA63 is not required in order to provide these epitopes. |
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ISSN: | 0264-410X 1873-2518 |
DOI: | 10.1016/j.vaccine.2005.10.018 |