Zusammenfassung der Ressource
Zaite Ebola Virus
- Background
- According to the WHO, the viral
outbreak has led to 2240 suspected
and con- firmed cases and 1229
deaths in four countries: Guinea,
Liberia, Nigeria, and Sierra Leone
- Family: Filoviridae
- OTher Categories
- Target
- Humans besides Zaire
- Bundibugyo virus
- Sudan virus
- Taï Forest virus
- Non-Human Primates
- Reston virus
- Identified in 1976 and
named after the Ebola
River where the first
known epidemic occurred
- References:
- Zhang YF, Li DP, Jin X, Huang Z.
Fighting Ebola with ZMapp: spotlight
on plant-made antibody. Sci China
Life Sci, 2014, 57: 1–3, doi:
10.1007/s11427-014-4746-7
- Endothelial Cells in Physiology and in the Pathophysiology of
Vascular Disorders in
http://www.bloodjournal.org/content/91/10/3527?sso-checked=true.
- Institute for Molecular Bioscience, University of
Queensland, Q4072, Australia.
D.Hume@imb.uq.edu.au. The MPS in
http://www.ncbi.nlm.nih.gov/pubmed/16338128.
- Hepatic Histology in
http://www.vivo.colostate.edu/hbooks/pathphys/digestion/liver/histo_hcytes.html
- Seasonal Influenza
Infection Control
Guidelines 2010
- CDC in
http://www.cdc.gov/flu/professionals/infectioncontrol/index.htm
- CDPH
http://www.cdph.ca.gov/programs/immunize/Documents/CDPHGuidanceFluPreventionHCS20101105.pdf
- Cal/OSHA
http://www.dir.ca.gov/dosh/Cal-OSHA_influenza_guidance_11-5-10.pdf
- Monoclonal antibody drugs for cancer in
http://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808
- Fatality Rate: 90%
- the proportion of deaths
within a designated
population of "cases"
- Infection
- Steps of infection
- Step 1
- Endothelial Cells
- ECs line vessels in every organ system
and regulate the flow of nutrient
substances, diverse biologically active
molecules, and the blood cells
themselves.
- Mononuclear Phagocytes
- Defined as a family of cells comprising
bone marrow progenitors, blood monocytes
and tissue macrophages. Macrophages are
a major cell population in most of the
tissues in the body.
- Hepatocytes
- Cells of the liver that perform
an astonishing number of
metabolic, endocrine and
secretory functions
- Step 2
- Evade the host immune
system
- Step 3
- Damages internal tissues and organs,
such as blood vessels and the liver: ultimately
death.
- Transmission
- Contact with Body Fluids
- Aerosol infection not
proved clinically
- Droplets: land directly on mucosal lining of nose,
mouth, eyes of nearby persons or can be inhaled.
Highest exposures within 3-6 feet.
- Airborne: aerosols become smaller by evaporation;
small aerosols (≤ 10 microns) remain suspended for
longer periods, if inhaled travel deep into the lungs.
- Contact: Aerosols/ secretions contaminate
nearby surface. Touch surfaces can infect
self or others.
- Symptoms
- 2 - 21 days
- fever, muscle pain, diarrhea, vomiting
- 21< days
- haemorrhagic diathesis,
delirium and shock
- ZMapp
- Efficacy of 4/5 patients
- Experimental drug co-developed by Mapp
Biophamaceutical, Inc. (San Diego, CA, USA)
and Defyrus 2 Zhang. (Toronto,
Canada).
- Combination of three “humanized” monoclonal
antibodies (mAbs) against the EBOV GP protein.
- Monoclonal antibodies mimic the
antibodies your body naturally
produces as part of your immune
system's response to germs, vaccines
and other invaders.
- Produced in plant: 3
- MAbs produced in these glycomodified
plants had mammalian-like glycans with
more homogeneous glycoforms than that
produced in CHO cells
- Glycans: large number of monosaccharides linked glycosidically
- History
- Plant made antibody studies
- First Wave: Production of
monoclonal antibodies (1989)
- Transgenic Technology
- Delivery of genes of interest into plant cells,
subsequent integration of theses genes into the
parental plant chromosome, and selection of
stable transgenic plants.
- Stopped by a number of issues associated with this expression
strategy, including low expression levels, long timeframes to
generate transgenic plants, undesired glycosylation patterns, and
concerns on spreading transgenes into the environment
- Second Wave: replica- tion-competent viral
vectors, such as magnICON and Gemini
- These vectors contain elements required for viral replicon formation. Once delivered into plant cells via
Agrobacterium infiltration, these vectors are able to assem- ble into replicons, which undergo automatic
replication and result in a high copy number of RNA molecules encoding the desired antibody.
- Indoor production
- No spreading of recombinant
genes by pollination