G1SecL05: Difference between revisions

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== LA-2 FAB with OspA Complex ==
[[Image:1FJ1 Chain E.jpg|300px|right|thumb| 1FJ1 Chain E]]
[[Image:1FJ1 Chain E.jpg|300px|right|thumb| 1FJ1 Chain E]]


CONTENT
__TOC__
=='''Background'''==


1. Background
Lyme disease, discovered in 1975<ref>PMID: 17160599</ref>, is a vector--borne disease caused by the inoculation of spirochete borrelia into the skin by members of hard bodied ticks of the family Ixodidae. Symptoms include arthritis at major joints, neurological problems such as reduced memory and poor ability to concentrate, and characteristic lesions erythema migans, more commonly known as the bull’s eye rash. A major outer surface membrane protein of Borrelia, ospA, plays a key role in immunity against Lyme disease through its binding to the antibody LA-2 fab.
 
2. Introduction to the fab complex, LA-2 , some history, what is it etc?


3. Structural capabilities – loops – loop 1, loop 2, loop 3 brief overview s and exactly how does the ospA bind to the LA-2
=='''Development of the recombinant vaccine'''==


4. Variability – highlight Ala 208, trp 216, a hvl 217 -237 – basically our stories , a couple of sentences on each.
Initial approaches for vaccines to treat lyme disease solely focused on ospA after studies involving passive immunization in mice. Studies indicated that passive immunization in mice only occurred if the blood from humans infected with Lyme disease contained anti-ospA monoclonal antibodies<ref>PMID: 15864264</ref>.  Although ospA vaccines, such as Lymerix, were able to halt transmission of the spirochetes, they were immediately pulled from the market due to chronic side effects such as severe arthritis. Additionally, quantitative analysis of immune response<ref>PMID:11865439</ref> of the whole ospA indicated that it is not predictive of protection.


Background
Recent developments in vaccines against Lyme Borreliosis emphasize the need to utilize the LA-2 –ospA complex on the basis that it, as a result of its specificity, induces long- term immune response in mice during previously studied clinical trials. Passive immunization of mice that resulted with significant titers of LA-2 serum antibody had a strong correlation with protection against tick transmission of infection<ref>PMID: 23407755</ref>


Lyme disease, discovered in 1975<ref>PMID: 17160599</ref>, is a vector--borne disease caused by the inoculation of spirochete borrelia into the skin by members of hard bodied ticks of the family Ixodidae. Symptoms include arthritis at major joints, neurological problems such as reduced memory and poor ability to concentrate, and characteristic lesions erythema migans, more commonly known as the bull’s eye rash. A major outer surface membrane protein of Borrelia, ospA, plays a key role in immunity against Lyme disease through its binding to the antibody LA-2 fab.
=='''Inefficiency and concerns'''==
==''' Discussion'''==


Introduction to the LA-2 OspA


<Structure load='1fj1' size='500' frame='true' align='right' caption='3D Jmol model' scene='Insert optional scene name here' />
<Structure load='1fj1' size='500' frame='true' align='right' caption='3D Jmol model' scene='Insert optional scene name here' />
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<scene name='G1SecL05/1fj1-condensed/1'>Composite Three variable regions highlights, Tryptophan 216 - Blue, Alanine 208 - Purple, Highly Variable LA-2 Fab + OspA conjunction - Red</scene>
<scene name='G1SecL05/1fj1-condensed/1'>Composite Three variable regions highlights, Tryptophan 216 - Blue, Alanine 208 - Purple, Highly Variable LA-2 Fab + OspA conjunction - Red</scene>


=='''References'''==


==References==
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