User:Marvin O'Neal/OspA: Difference between revisions

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<span style="color:red">The membrane composition of <i>Borrelia</i> is abundant in both OspA and OspB, and the two proteins share a 53% similarity in their primary sequences. Both are also expressed in the tick's gut and downregulated during feeding and aid in its survivability; however, OspA is overall less varied and reactive than OspB, which has much more variability.<ref name="becker">PMID: 15713683</ref> The relatively conserved sequence of OspA thus better lends itself to study than that of OspB and applications toward the development of a vaccine for Lyme disease for a broader range of strains. The first vaccine developed used a purified recombinant form of OspA and functioned in blocking transmission of the spirochetes from tick to host during feeding, killing them while thus still attached and expressing OspA in the tick's gut.<ref name="connolly">PMID: 15864264</ref><ref name="battisti">PMID: 18779341</ref>
<span style="color:red">The membrane composition of <i>Borrelia</i> is abundant in both OspA and OspB, and the two proteins share a 53% similarity in their primary sequences. Both OspA and OspB are expressed in the tick's gut and downregulated during feeding and aid in its survivability; however, OspA is overall less varied and reactive than OspB, which has greater variability.<ref name="becker">PMID: 15713683</ref> The relatively conserved sequence of OspA thus lends itself better to study and application toward the development of a vaccine for a broader range of <i>Borrelia</i> strains in the treatment of Lyme disease than that of OspB. The first vaccine developed used a purified recombinant form of OspA and functioned in blocking transmission of the spirochetes from tick to host during feeding, killing them while thus still attached and expressing OspA in the tick's gut.<ref name="connolly">PMID: 15864264</ref><ref name="battisti">PMID: 18779341</ref>


Known as Lymerix, clinical trials had shown 76% and 92% effectiveness in treatment after two years when following a three-dose schedule. However, the vaccine was pulled from use in 2002 when opponents claimed the [http://en.wikipedia.org/wiki/Immunoglobulin_G IgG antibodies] for OspA were associated with the development of severe chronic arthritis, as well as other side effects affecting immunity.<ref name="connolly">PMID: 15864264</ref><ref name="plotkin">PMID: 21217175</ref> In conjunction with the desire for a more widespread vaccine treating multiple strains, research towards a new vaccine has been under development.
Known as Lymerix, clinical trials had shown 76% and 92% effectiveness in treatment after two years when following a three-dose schedule. However, the vaccine was pulled from use in 2002 when opponents claimed the [http://en.wikipedia.org/wiki/Immunoglobulin_G IgG antibodies] for OspA were associated with the development of severe chronic arthritis, as well as other side effects affecting immunity.<ref name="connolly">PMID: 15864264</ref><ref name="plotkin">PMID: 21217175</ref> In conjunction with the desire for a more widespread vaccine treating multiple strains, research towards a new vaccine has already begun.


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LYMErix, was discontinued in 2002 due to various weaknesses of the vaccine including its <80% efficacy, requirement for 3 doses, lack of data concerning the effects of the vaccine on children, and limitation of protection to the North American species of Borrelia. 6 To address this problem of international protection it would be helpful to create a chimera, mixing the OspA of different species. In order to do this the epitope of OspA should be studied. LA-2 <<SHOW FAB HIGHLIGHTED ON 1FJ1>> is a murine monoclonal antibody that binds strongly <<SHOW INTERACTION HIGHLIGHTED (ZOOMED IN) ON 1FJ1>> to OspA <<SHOW OSPA HIGHLIGHTED ON 1FJ1>>, and how effective a vaccine is correlated with LA-2 binding. 5
 
 
To address this problem of international protection it would be helpful to create a chimera, mixing the OspA of different species. In order to do this the epitope of OspA should be studied. LA-2 <<SHOW FAB HIGHLIGHTED ON 1FJ1>> is a murine monoclonal antibody that binds strongly <<SHOW INTERACTION HIGHLIGHTED (ZOOMED IN) ON 1FJ1>> to OspA <<SHOW OSPA HIGHLIGHTED ON 1FJ1>>, and how effective a vaccine is correlated with LA-2 binding. 5
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<ref name="nigrovic">PMID: 16893489</ref>
<ref name="nigrovic">PMID: 16893489</ref>


<li>4 Battisti JM,  Bono JL,  Rosa PA, et al. 2008. Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector. Infect. Immun. 76(11): 5228-5237.<br>
<li>4 (now 6) Battisti JM,  Bono JL,  Rosa PA, et al. 2008. Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector. Infect. Immun. 76(11): 5228-5237.<br>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2573341/<br>
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2573341/<br>
PMID: 18779341
PMID: 18779341
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<ref name="ding">PMID: 11183781</ref>  
<ref name="ding">PMID: 11183781</ref>  


<li>6 Plotkin S. 2011. Clinical Infectious Diseases. Correcting a Public Health Fiasco: The Need for a New Vaccine Against Lyme Disease. 52(3):s721-275.<br>
<li>6 (now 7) Plotkin S. 2011. Clinical Infectious Diseases. Correcting a Public Health Fiasco: The Need for a New Vaccine Against Lyme Disease. 52(3):s721-275.<br>
http://cid.oxfordjournals.org/content/52/suppl_3/s271.full<br>
http://cid.oxfordjournals.org/content/52/suppl_3/s271.full<br>
PMID: 21217175
PMID: 21217175