G18secL03Tpc4: Difference between revisions
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Unlike OspC, the OspA protein is only present in the ''Borrelia burgdorferi'' while they are in the midgut of the cold blooded tick, and not in the host. Once the tick begins to feed on its warm blooded mammalian host, the ''Borrelia burgdorferi'' migrate from the midgut of the tick to the salivary glands and OspC is produced in the host's bloodstream. <ref name="Green">D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> Because of this, when a host is vaccinated with the OspA vaccine, antibodies to the OspA protein can only kill the bacteria inside of the tick if it ingests the antibodies during feeding. <ref name="Green"/> If the bacteria enter the host, it can differentiate into several forms for which the vaccine cannot protect against. In contrast, an OspC based vaccine would allow the host to make antibodies to kill the Borrelia burgdorferi after they enter the host's body. <ref name="Green"/> | Unlike OspC, the OspA protein is only present in the ''Borrelia burgdorferi'' while they are in the midgut of the cold blooded tick, and not in the host. Once the tick begins to feed on its warm blooded mammalian host, the ''Borrelia burgdorferi'' migrate from the midgut of the tick to the salivary glands and OspC is produced in the host's bloodstream. <ref name="Green">D. Greenburg, M.S. Rowe. Brookhaven Scientists Determine Key Lime Disease Protein Structure.Brookhaven National Laboratory (2001)[http://www.bnl.gov/bnlweb/pubaf/pr/2001/bnlpr022801.htm]</ref> Because of this, when a host is vaccinated with the OspA vaccine, antibodies to the OspA protein can only kill the bacteria inside of the tick if it ingests the antibodies during feeding. <ref name="Green"/> If the bacteria enter the host, it can differentiate into several forms for which the vaccine cannot protect against. In contrast, an OspC based vaccine would allow the host to make antibodies to kill the Borrelia burgdorferi after they enter the host's body. <ref name="Green"/> | ||
==== Main Problems with Application of OspC-based Vaccine ==== | ==== Main Problems with Application of OspC-based Vaccine ==== | ||
The major problem with creating an OspC based vaccine is a lack of knowledge regarding the three dimensional structure of the different variants of the OspC protein, especially those from invasive strains. <ref name="Green"/> The OspC locus of Borrelia burgdorferi is much more variable than other genes in the species. There are 22 OspC major groups, with 15 of those found in the northeastern United States. <ref | The major problem with creating an OspC based vaccine is a lack of knowledge regarding the three dimensional structure of the different variants of the OspC protein, especially those from invasive strains. <ref name="Green"/> The OspC locus of Borrelia burgdorferi is much more variable than other genes in the species. There are 22 OspC major groups, with 15 of those found in the northeastern United States.<ref name="Brisson"/> In a recent study run by researchers at the University of California Davis, it was found that OspA genes from 3 isolates were greater than 99% homologous, while OspC genes shared only 81%-85% homology. <ref name="Cadiz">R.B. Cadiz, M. Crawford, R.B. LeFebvre, W.S Probert. Immunization with Outer Surface Protein (Osp) A, but Not OspC, Provides Cross-Protection of Mice Challenged with North American Isolates of ''Borrelia'' ''Burgdorferi''. The Journal of Infectious Diseases 1997; Volume 175: 400-405. [http://www.jstor.org/discover/10.2307/30131660?uid=3739832&uid=2&uid=4&uid=3739256&sid=21101134072011]</ref> The genetic and antigenic heterogeneity associated with OspC, but not OspA, may limit the effectiveness of an OspC based vaccine, since the vaccine would not protect against all of the strains. <ref name="Cadiz"/> | ||
=== Necessity of Further Research on OspC === | === Necessity of Further Research on OspC === | ||
The biological function of OspC is not yet completely understood. Further investigation is required to determine OspC ecology and its relatedness to the pathogenicity of ''B. Burgdorferi''. For the development of an effective OspC-based vaccine, it is important to know representative three-dimensional structures of at least a few more OspCs, especially those from the invasive strains. This information could be useful for rational design of an OspC-based recombinant vaccine.<ref name="Kum"/> Also, further understanding of the evolution and genetics of Lyme Disease cause, ''Borrelia burgdorferi'', with its outer surface proteins such as OspC, fosters progress toward ecologically based control efforts.<ref>PMID:20877579</ref> | The biological function of OspC is not yet completely understood. Further investigation is required to determine OspC ecology and its relatedness to the pathogenicity of ''B. Burgdorferi''. For the development of an effective OspC-based vaccine, it is important to know representative three-dimensional structures of at least a few more OspCs, especially those from the invasive strains. This information could be useful for rational design of an OspC-based recombinant vaccine.<ref name="Kum"/> Also, further understanding of the evolution and genetics of Lyme Disease cause, ''Borrelia burgdorferi'', with its outer surface proteins such as OspC, fosters progress toward ecologically based control efforts.<ref>PMID:20877579</ref> | ||
