ZMapp is an experimental biological product developed by the United States and Canada , which was introduced in August 2014 as a medicine for the Ebola Hemorrhagic Epidemic Outbreak that broke out this year in several countries of West Africa. It consists of three humanized (ie, recombinant, containing elements of a human immunoglobulin to reduce the immune response when introducing antibodies originally obtained from animals to humans) [1] monoclonal antibodies obtained by hybridoma technology [2] [3] .
Content
- 1 Development
- 2 Production
- 3 Application
- 4 notes
Development
The creation of the drug is carried out by the company Mapp Biopharmaceutical from the California city of San Diego [4] , the US government and the Canadian Department of Health [5] . This development was born on the basis of a program for obtaining drugs from antibodies, which has been carried out in the United States for more than ten years to protect its military personnel [6] and long-term funding by the Canadian Health Department [7] .
Two of the three humanized monoclonal antibodies (English mAbs) in the preparation were taken from a combination of ZMAb antibodies (obtained by Defyrus / PHAC), and the third from MB-003 (obtained by Mapp) [6] .
According to the authors of the study, during experimental infection with the Ebola virus of rhesus monkeys , in the case of treatment with this drug no later than 5 days after infection, the survival rate of animals was 100%, despite the fact that many patients had serious manifestations of the disease, such as significant an increase in body temperature, the presence of a virus in the blood (viremia), abnormalities in the number of blood cells and the biochemical composition of blood. The severe course of the disease, manifested in an increase in the number of liver enzymes, bleeding from the mucous membranes and generalized petechiae (the smallest hemorrhages on the skin as a result of rupture of capillaries [8] [9] ), turned out to be reversible with the complete recovery of animal patients [2] .
Production
(1) immunization of animals;
(2) isolation of B lymphocytes from the spleen;
(3) myeloma cell culture;
(4) the fusion of b-lymphocytes and myeloma cells;
(5) segregation of cell lines;
(6) screening and selection of antibody producing lines;
(7) propagation of the hybridoma in vitro (a) or in vivo (b) ;
(8) obtaining antibodies.
The initial number of antibodies to the virus is obtained by hybridoma technology. With this method, mice are injected with a virus, they develop an immune response, B-lymphocytes are secreted from their spleen, which merge with tumor cells - myeloma cells, after which screening and selection of cell lines producing antibodies are performed to select the best antibodies. After selecting such an antibody, the gene that encodes it is isolated, and then the antibody is humanized (replaces the parts of the protein chain that are characteristic of the animal from which it was obtained with those of a person) to avoid an allergic reaction.
For the subsequent propagation of the hybridoma in the case of ZMapp, genetically modified tobacco plants were used, which began to produce the corresponding antibodies . The modification ( transfection ) of the genetic apparatus of tobacco plants was carried out by a specially selected viral infection carrier - a culture of the virus-infected bacterium Agrobacterium tumefaciens , known for its ability to incorporate parts of its DNA into plant DNA and therefore important for genetic engineering in agrobiology. Then the desired antibodies are obtained from the plants.
Application
On the developer's site at the end of August 2014, it was stated that the drug was nominated to become a cure for Ebola in January of the same year, but that its use in humans has not yet been authorized by the American authorities because of the lack of research into its effectiveness and safety in humans and that the company does not yet have a sufficient amount of the drug [5] .
In August 2014 reported two American ZMapp cured physicians [10] [11] (the main physician of Samaritan's Purse Liberian Medical Center, Dr. Kent Brentley, and the Serving in Mission missionary (SIM) Dr Nancy Wright) Kent Brantly and Nancy Writebol) from Emory University in Atlanta , Georgia ), assisting the people of Liberia. [12]
According to the U.S. Centers for Disease Control and Prevention , the experimental treatment of its volunteers was ordered by Samaritan's Purse, which contacted the CDC. The CDC linked the applicants to the National Institutes of Health (NIH ), and there they were associated with a private drug company. As a result, US government organizations did not directly participate in the treatment with the drug, the effectiveness and safety of which have not been proven, as a result of which it has not yet received permission for use in humans. It also states with reference to the manufacturer that so far only the minimum number of doses of the drug has been received and all of them are being used, and that it is not yet possible to place an order for new ones. It also states that according to the regulations of the US Food and Drug Administration (FDA), in exceptional cases, the use of innovative drugs that have not yet passed the full cycle of clinical trials may be allowed [13] .
The doctor also received a blood transfusion of a 14-year-old teenager who survived the infection under the guidance of this doctor and was grateful to him [14] . When analyzing the observations of the 1995 epidemic, it turned out that even then the life of 7 out of 8 sick physicians was saved by immunization with the help of a blood transfusion that successfully survived the disease, but this method did not become generally accepted during the current epidemic due to its poorly studied relevance to this disease [ 15] .
The use of a severely deficient, but potentially effective drug to save the lives of just foreigners - representatives of the white race, traditionally associated in Africa with the ideas of colonialism, raised doubts about the ethics of this step among the public and forced President Samaritan's Purse to confirm in the press the correctness of the choice made. The organization considered its selfless and faithful doctor to be absolutely worthy of the cure for which it was praying, and the cure and the absence of serious side effects due to the lack of research of the drug were far from guaranteed. The initiator of the discussion, the author of the answer presented as people living in the United States in favorable conditions and far from the idea of going to Africa to provide real assistance. The president of the organization reports that there were only three doses of the drug, of which two were received in Liberia by Ms. Raytball, and the third was given to the doctor [16] .
Earlier it was reported that treatment with the help of ZMapp of a Spanish priest, who worked and became infected in Liberia, was unsuccessful and the disease ended in death [17] [18] .
Notes
- ↑ Humanized antibodies (humanized antibodies) http://humbio.ru/humbio/tarantul_sl/000006fb.htm
- ↑ 1 2 Qiu, Xiangguo. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp: [ eng. ] / Xiangguo Qiu, Gary Wong, Jonathan Audet ... [et al. ] // Nature: j. - 2014 .-- Vol. 514, no. 7520 (October 2). - P. 47-53. - DOI : 10.1038 / nature13777 . - PMID 25171469 . - PMC PMC4214273 .
- ↑ Innocent, Irina. The medicine against Ebola showed the first results // Russian newspaper. - 2014 .-- August 30.
- ↑ Morin, Monte. Mystery Ebola virus serum manufactured by San Diego firm : [ eng. ] // Los Angeles Times. - 2014 .-- 4 August.
- ↑ 1 2 ZMapp ™ Information Sheet : [ eng. ] : [ arch. August 12, 2014 ] / LeafBio. - Mapp Biopharmaceutical. - (inaccessible link) .
- ↑ 1 2 Langreth, Robert. Ebola Drug Made From Tobacco Plant Saves US Aid Workers : [ eng. ] / Robert Langreth, Caroline Chen, James Nash ... [ et al. ] // Business Week. - 2014 .-- 4 August.
- ↑ Branswell, Helen. Experimental Ebola drug based on research discoveries from Canada's national lab : [ eng. ] : [ arch. August 10, 2014 ] // The Brandon Sun. - 2014 .-- 5 August.
- ↑ Petechia // Great Soviet Encyclopedia : [in 30 vol.] / Ch. ed. A.M. Prokhorov . - 3rd ed. - M .: Soviet Encyclopedia, 1969-1978.
- ↑ Petechia // Medical Encyclopedia .
- ↑ Ebola crisis : Doctors in Liberia "recovering after taking ZMapp": [ eng. ] : [ arch. August 19, 2014 ] // BBC. - 2014 .-- 19 August.
- ↑ Baklanov, Alexander. A doctor from the USA Recovered from an Ebola virus . Snob (August 21, 2014). Date accessed August 17, 2019. Archived August 22, 2014.
- ↑ Justice, Elaine Emory University Hospital Ebola team featured by NBC News . Emory News center (September 3, 2014). Date of treatment August 18, 2019.
- ↑ Q&A on Experimental Treatments and Vaccines for Ebola . Ebola Hemorrhagic Fever (inaccessible link) . CDC Archived on August 8, 2014.
- ↑ 'A Miraculous Day' . Dr. Kent Brantly credits God for his recovery from the Ebola virus as he is released from Emory University Hospital . Samaritan's Purse (August 21, 2014) . Date accessed August 17, 2019.
- ↑ Wolfson, Elijah. The 20-Year-Old Ebola Treatment That Could Save Kent Brantly : [ eng. ] // Newsweek. - 2014 .-- 1 August.
- ↑ Graham, Franklin Franklin Graham: Saving Ebola doctor no ethical dilemma . USQ Today (August 21, 2014). Date accessed August 17, 2019.
- ↑ Baklanov, Alexander The third European Was killed by Ebola . Snob (August 12, 2014). Date accessed August 17, 2019.
- ↑ Álvarez, P. Muere el sacerdote Miguel Pajares, el primer fallecido por ébola en Europa : El cuerpo del religioso ha sido incinerado sin que se le practicase la autopsia: [ Spanish ] : [ arch. August 13, 2014 ] / P. Álvarez, MA Torres // EL PAÍS. - 2014 .-- 12 agosto.