Viral Enfeksiyonlar ile Mücadelede En Hızlı Silahlardan Biri: Antiserum/Plazma Tedavisi

Öz

SARS-CoV-2’nin neden olduğu COVID-19 pandemisi, bulunduğumuz zaman diliminde hızla dünya popülasyonu arasında yayılmaya devam etmektedir. 2020 yılı ve 2021 yılı başlarında ortaya çıkan yeni mutant ve varyantlar virusa karşı mücadelede handikaplar yaratmaktadır. Özellikle akut enfekte olan bireylerde tedavi için acil olarak kullanılan ilaçların tam olarak standardize edilememesi bilim dünyasını bu salgın ve gelecekteki salgınlar için arayışlara yöneltmiştir. Bu araştırmalarda tarihte elde edilen kanıtlara ve verilere dayalı olarak bazı uygulamalar ön plana çıkmaktadır. Bu uygulamalardan en çok bilineni ve tarihte hemen her virus salgınında acil olarak tedavide kullanılan yöntem “antiserum” ya da “konvelesan plazma tedavisi”dir. Bu tedavi biçiminde amaç; iyileşen hastanın serum/plazmasında bulunan nötralizan antikorlar hasta olan bireye verilerek virusun nötralize edilmesini sağlamaktır. Antiserum ve konvelesan plazma tedavisinin transfüzyonel bazlı olup bireye ve/veya ürüne bağlı bazı yan etkilerinin ortaya çıkabilme ihtimali ve nötralizan antikor içeriği bakımından serumun standardize edilememe gibi majör sorunları mevcuttur. Bu yüzden COVID-19 salgınında bilim insanları daha spesifik olarak SARS-CoV-2’ye karşı monoklonal antikor üreterek ve yan etkileri mümkün olduğunca minimize ederek hedefe kilitlenen bir tedavi yöntemi geliştirmeyi hedeflemişlerdir. Elde edilen monoklonal antikorlar farklı farklı olabilmektedir. Bu monoklonal antikorların belli oranda karıştırılarak hastaya verilmesine “antikor kokteyli” tedavisi denir. Geleneksel yöntem antiserum-plazma tedavisi başta olmak üzere antikor bazlı yeni nesil ilaçlar geçmişteki salgınlarda ve COVID-19 pandemisinde kullanımları, elde edilen sonuçlar bu makalede derlenmiştir.

Anahtar Kelimeler

• Antiserum
• COVID-19
• Plazma
• SARS-CoV-2
• Virus

One of the Fastest Weapons against Viral Infections: Antiserum/Plasma Therapy

Öz

COVID-19 pandemic caused by SARS-CoV-2 continues to spread rapidly among the world population in the recent time period. New mutants and variants that emerged in 2020 and early 2021 create handicaps in the struggle against the virus. The inability to fully standardize the drugs used urgently for treatment, especially in acutely infected individuals, has led the scientific world to search for this epidemic and future epidemics. In these studies, some applications come to the forefront based on the evidence and data obtained in history. The most well-known of these applications and the method used in the emergency treatment of almost every virus epidemic in history is "antiserum" or "convalescent plasma therapy". In this form of treatment, the aim is; Neutralizing antibodies in the serum/plasma of the recovered patient are given to the sick individual to ensure that the virus is neutralized. Antiserum and convalescent plasma therapy are transfusion-based and have major problems such as the possibility of some side effects depending on the individual and/or product, and the inability to standardize the serum in terms of neutralizing antibody content. Therefore, in the COVID-19 epidemic, scientists aimed to develop a targeted treatment method, more specifically by producing monoclonal antibodies against SARS-CoV-2 and minimizing side effects as much as possible. Obtained monoclonal antibodies can be different. The administration of these monoclonal antibodies to the patient by mixing them in a certain ratio is called “antibody cocktail” therapy. The use of antibody-based new-generation drugs, especially the traditional method antiserum-plasma therapy, in past epidemics and the COVID-19 pandemic, and the results obtained are compiled in this article.

Anahtar Kelimeler

• Antiserum
• COVID-19
• Plasma
• SARS-CoV-2
• Virus

Kaynakça

1. Anonim (2017) WHO, World Health Organization. Other rabies biological products. Erişim adres: https://www.who.int/rabies/resources/other_rabies_biolog_product/en/, Erişim tarihi: 14.05.2021
2. Anonim. (2018) FDA, Science and the regulation of biological products. Erişim adresi: https://www.fda.gov/about-fda/histories-product-regulation/science-and-regulation-biological-products, Erişim tarihi: 08.05.2021
3. Anonim. (2018a) Türk Neonatoloji Derneği Palivizumab ile RSV Proflaksisi Önerileri. Erişim adresi: http://www.neonatology.org.tr/wp-content/uploads/2020/04/TND-PalivizumabileRSVProflaksisiOnerileri-2018.pdf, Erişim tarihi: 12.05.2021
4. Anonim. (2020) BBC News: Dexamethasone, remdesivir, Regeneron: Trump's Covid treatment explained. Erişim adresi: https://www.bbc.com/news/health-54418464, Erişim tarihi: 11.05.2021
5. Anonim. (2021) Clinical Trials Arena. Celltrion’s regdanvimab neutralises South African Covid-19 variant. Erişim adresi: https://www.clinicaltrialsarena.com/news/celltrion-regdanvimab-south-african-variant/, Erişim tarihi: 10.05.2021
6. Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, et al. (2015). Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 4, 709. http://dx.doi.org/10.1186/s40064-015-1490-9.
7. von Behring E, Kitasato S. (1991). The mechanism of diphtheria immunity and tetanus immunity in animals. 1890. Mol Immunol. 28, 1319–1320.
8. Bren L. (2006). The road to the biotech revolution: highlights of 100 years of biologics regulation. FDA Consum. 40, 50–57.

9. Center for Disease Control and Prevention (CDC). (2021). Influenza; Influenza Antiviral Medications: Summary for Clinicians. Erişim adresi: https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm#overview, Erişim tarihi: 15.05.2021
10. Cheng FWT, Ng PC, Chiu WK, Chu WCW, Li AM, Lo KL, Hon EKL, Nelson EAS, Leung TF, Ng WH, et al. (2005). A case-control study of SARS versus community acquired pneumonia. Arch Dis Child. 90, 747–749. http://dx.doi.org/10.1136/adc.2004.063446.
11. FDA U.S. Food and Drug Administration (2021). Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab. Erişim adresi: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-monoclonal-antibody-bamlanivimab, Erişim tarihi: 12.05.2021
12. Garraud O, Heshmati F, Pozzetto B, Lefrere F, Girot R, Saillol A, Laperche S. (2016). Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow. Transfus Clin Biol. 23, 39–44. http://dx.doi.org/10.1016/j.tracli.2015.12.003. Gerlach M, Proksch AL, Unterer S, Speck S, Truyen U, Hartmann K. (2017). Efficacy of feline anti-parvovirus antibodies in the treatment of canine parvovirus infection. J Small Anim Pract. 58, 408–415. http://dx.doi.org/10.1111/jsap.12676.
13. Gould EW. (1919). Human serum in the treatment of influenza bronchopneumonia. N Y Med J. 109, 666–667.
14. van Griensven J, Edwards T, Baize S, Ebola-Tx Consortium. (2016). Efficacy of convalescent plasma in relation to dose of Ebola virus antibodies. N Engl J Med. 375, 2307–2309. http://dx.doi.org/10.1056/NEJMc1609116.
15. Hey A. (2015). History and practice: Antibodies in infectious diseases. Microbiol Spectr. 3, AID-0026-2014. http://dx.doi.org/10.1128/microbiolspec.AID-0026-2014.
16. Joyner M, Wright RS, Fairweather D, Senefeld J, Bruno K, Klassen S, Carter R, Klompas A, Wiggins C, Shepherd JR, et al. (2020). Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. J Clin Invest. 130, 4791-4797. https://doi.org/10.1172/JCI140200.
17. Kahn MH. (1919). Serum treatment of postinfluenzal bronchopneumonia. J Am Med Assoc. 72, 102–103.
18. Klassen SA, Senefeld JW, Johnson PW, Carter RE, Wiggins CC, Shoham S, Grossman BJ, Henderson JP, Musser J, Salazar E, et al. (2021). The effect of convalescent plasma therapy on mortality among patients with COVID-19: Systematic review and meta-analysis. Mayo Clin Proc. 96, 1262–1275. http://dx.doi.org/10.1016/j.mayocp.2021.02.008.
19. Koç BT. (2020). Current clinical trials and vaccine development. Eurasian J Vet Sci, COVID-19 Special Issue, 91-98. http://dx.doi.org/10.15312/EurasianJVetSci.2020.299.
20. Kong LK, Zhou BP. (2006). Successful treatment of avian influenza with convalescent plasma. Hong Kong Med J. 12, 489. https://www.ncbi.nlm.nih.gov/pubmed/17148811.
21. Lesne E, Brodin P, Saint-Girons F. (1919) Plasma therapy in influenza. Presse Med. 27, 181–182.
22. Lindenmann J. (1984). Origin of the terms “antibody” and “antigen.” Scand J Immunol. 19, 281–285.
23. Luke TC, Casadevall A, Watowich SJ, Hoffman SL, Beigel JH, Burgess TH. (2010). Hark back: passive immunotherapy for influenza and other serious infections. Crit Care Med. 38, 66-73. http://dx.doi.org/10.1097/CCM.0b013e3181d44c1e.
24. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw F-M, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR, et al. (2015). The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 211, 80–90.
25. Montelongo-Jauregui D, Vila T, Sultan AS, Jabra-Rizk MA. (2020). Convalescent serum therapy for COVID-19: A 19th century remedy for a 21st century disease. PLoS Pathog. 16, e1008735. http://dx.doi.org/10.1371/journal.ppat.1008735.
26. O'Malley J, Hartman F. (1919). Treatment of influenzal pneumonia with plasma of convalescent patients. J Am Med Assoc. 72, 34–37.
27. Moore C, Galiano M, Lackenby A, Abdelrahman T, Barnes R, Evans MR, Fegan C, Froude S, Hastings M, Knapper S, et al. (2011). Evidence of person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus in a hematology unit. J Infect Dis. 203, 18–24. http://dx.doi.org/10.1093/infdis/jiq007.
28. Pelegrin M, Naranjo-Gomez M, Piechaczyk M. (2015). Antiviral monoclonal antibodies: Can they be more than simple neutralizing agents? Trends Microbiol. 23, 653–665. http://dx.doi.org/10.1016/j.tim.2015.07.005. Pizzorno A, Bouhy X, Abed Y, Boivin G. (2011). Generation and characterization of recombinant pandemic influenza A(H1N1) viruses resistant to neuraminidase inhibitors. J Infect Dis. 203, 25–31. http://dx.doi.org/10.1093/infdis/jiq010.
29. Sivapalasingam S, Saviolakis GA, Kulcsar K, Nakamura A, Conrad T, Hassanein M, Sumner G, Elango C, Kamal MA, Eng S, et al. (2021). Human monoclonal antibody cocktail for the treatment or prophylaxis of Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV). J Infect Dis. jiab036. http://dx.doi.org/10.1093/infdis/jiab036.
30. Skarbinski J, Jain S, Bramley A, Lee EJ, Huang J, Kirschke D, Stone A, Wedlake T, Richards SM, Page S, et al. (2011). Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009. Clin Infect Dis. 52, 50-59. http://dx.doi.org/10.1093/cid/ciq021.