OspA L03 Group2
IntroductionIntroduction
Lyme disease has been affecting many individuals year around developing chronic arthritis, neurologic and cardiac abnormalities, and skin lesions (Burgdorferi, 1982). The bacterial vector, Borrelia burgdorferi is spread through the bite and feeding of ticks bringing initial severe skin lesions, erythema chronicum migrans within 10-12 weeks of infestation (Burgdorferi, 1982). Studies were first conducted through New Zealand white rabbits (Burgdorferi, 1982) through the use of indirect immunofluoresence.
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Outer surface protein A, or OspA is found to inhibit bacterial transmission [1]. Outer surface protein A, or OspA was found to initiate an immune response that contributed towards the development of Lyme disease vaccinations. It prevented the transmission of Borrelia burgdorferi, the causative bacterial agent of Lyme disease after the attachment of an infected tick [1]. Once entered the host through the skin or blood stream, Borrelia burgdorferi downregulated and suppressed OspA to minimize all of the host’s immunogenic characteristics [2]. When OspA on the spirochete migrated to an inflammatory environment, it induced apoptosis on the bacteria through the activation of B-cells [2]. Only OspA positive in borrelia bacteria were unable to establish an infection compared to OspA negative bacteria successfully hosted in studies of mice [2]. OspA known as a potent stimulator of neutrophils was able to kill the pathogen and attract leukocytes allowing the release of proinflammatory cytokines in a host [2] and avoid contracting Lyme disease as it affects the heart, joints, and nervous system [2]. The reactive LA-2 antibody was found to serve as an important epitope of Osp-A binding [1] towards developing vaccinations. The free state of the 3D model exposed the C-terminal where there were 49 residues from the “three loops” involved that significantly affected by LA-2 binding, through findings from NMR and crystallization [1].
About OspAAbout OspA
StructureStructure
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The model presented by the Protein Data Bank is OspA containing two light chains or Hybridoma Antibody LA2 (chains A and C), two heavy chains or Hyrbridoma Antibody LA2 (chains B and D), and two outer surface protein A (chains E and F).
The reactive LA-2 antibody was found to serve as an important epitope of Osp-A binding [1] towards developing vaccinations. The protein, OspA obtained from PDB was dissected to isolate and concentrate the F chain from the molecule of OspA from the crystallized structure to show the free state of the 3D model exposed the C-terminal.
There were 49 residues from the “three loops” involved that significantly affected by LA-2 binding, through findings from NMR and crystallization [1]. Residues 207 and 227 from “loop 1” were excluded from analysis because of the peak overlap [1]. The portion of the protein chain detected through 15N-HSQC NMR that were affected by the binding of LA2 [1] was highlighted.Residues 203 to 220 in “loop1” were represented by pale green, residues 224 to 233 in “loop 2” were colored purple and residues 246 to 257 in “loop 3” were colored medium slate blue. The cool coloring of the residues shows the location of LA-2’s direct contact on the “3 loops”. Primary colors were used to represent Ala208 as red and as blue in spacefills for the primary or initial identification of the LA-2 epitope on the beta-strands. The coloration of resides are all at one end, C-terminal of the isolated OspA molecule showing the side where LA-2 binds. The rest of the model were beta-sheets that were left yellow, as the neutral color, and the only alpha-helix was colored pink, to show the general overall structure of 21 anti-parrallel beta-strands to 1 alpha-helix [1].
Vaccination (La-2)Vaccination (La-2)
OspA is the least variable protein located on the outer surface of the borrelia bacteria [1]. This results in fewer mutations to occur allowing the same vaccine to stay in use for a longer time. Individuals who were bit by an infected tick and received the ospA vaccine were able to produce anti-opsA antibodies. These antibodies enter the tick through its blood meal into the gut where spirochetes are found and are destroyed by the antibody’s detection of opsA. Therefore, before the spirochete enters the host, it will be inactivated and Lyme Disease may be prevented (Marks, 2011).
The complement system of the host also has a beneficial effect on destroying the borrelia located in the tick’s gut. It works by opsonizing these pathogens and attracting leukocytes which are a main component of the defense system against pathogens [2].
Side EffectsSide Effects
Recent studies however have shown that neurological complications may appear in patients with this vaccination. This occurs because the down regulation of ospA from the vaccine would not be an abundant amount to activate the immune system for defense (Marks, 2011). This may then cause a wide range of adverse events such as headaches and acute neuroborreliosis(Marks, 2011).
Comparing OspA , OspB , OspCComparing OspA , OspB , OspC
References:
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 Ding W, Huang X, Yang X, Dunn JJ, Luft BJ, Koide S, Lawson CL. Structural identification of a key protective B-cell epitope in Lyme disease antigen OspA. J Mol Biol. 2000 Oct 6;302(5):1153-64. PMID:11183781 doi:10.1006/jmbi.2000.4119
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Rupprecht TA, Koedel U, Fingerle V, Pfister HW. The pathogenesis of lyme neuroborreliosis: from infection to inflammation. Mol Med. 2008 Mar-Apr;14(3-4):205-12. PMID:18097481 doi:10.2119/2007-00091.Rupprecht