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Szczepionki I Leki Stosowane W Terapii COVID-19

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Szczepionki I Leki Stosowane W Terapii COVID-19 TERAPIA I LEKI Szczepionki i leki stosowane w terapii COVID-19 Jolanta B. Zawilska1, Katarzyna Kuczyńska1, Magdalena Gawior2, Martyna Kosiorek2, Katarzyna Dąbrowska2, Zuzanna Dominiak2, Amelia Baranowska2, Gabriela Skorupska2, Agnieszka Sujecka2, Klaudia Michalak2, Agata Rojek2, Adrianna Bakowicz2, Weronika Kowalczyk2, Aleksandra Wojciechowska2, Wiktoria Bęczkowska2, Patryk Maj2 1Zakład Farmakodynamiki, Wydział Farmaceutyczny, Uniwersytet Medyczny w Łodzi, Polska 2Uniwersytet Medyczny w Łodzi (student), Polska Farmacja Polska, ISSN 0014-8261 (print); ISSN 2544-8552 (on-line) Adres do korespondencji Konflikt interesów Jolanta B. Zawilska, Zakład Farmakodynamiki, Nie istnieje konflikt interesów. Wydział Farmaceutyczny, Uniwersytet Medyczny w Łodzi, ul. Muszyńskiego 1, 90-151 Łódź, Polska; Otrzymano: 2021.03.03 e-mail: [email protected] Zaakceptowano: 2021.03.30 Opublikowano on-line: 2021.04.08 Źródła finansowania Uniwersytet Medyczny w Łodzi, DOI Grant No. 503/3-011-01/503-31-002-19. 10.32383/farmpol/135224 ORCID Therapy of COVID-19: vaccines and drugs Jolanta Barbara Zawilska (ORCID iD: 0000-0002-3696-2389) The COVID-19 pandemic, caused by SARS-CoV-2 – a novel and highly Katarzyna Kuczyńska (ORCID iD: 0000-0003-3103-5874) infectious coronavirus, has been spreading around the world for over a year, Magdalena Gawior (ORCID iD: 0000-0001-8418-1467) and poses a serious threat to the public health. Numerous studies have Martyna Kosiorek (ORCID iD: 0000-0002-2133-7054) revealed the genome, structure and replication cycle of the SARS-CoV-2 virus Katarzyna Dąbrowska as well as the immune response to infection. Data from these studies provide (ORCID iD: 0000-0002-0782-194X) a firm basis for the development of strategies to prevent the further spread Zuzanna Dominiak (ORCID iD: 0000-0003-0917-7286) of COVID-19, as well as to synthesize effective and safe vaccines and drugs. Amelia Baranowska (ORCID iD: 0000-0003-4915-3131) First and foremost, vaccines are needed to control the COVID-19 pandemic. Gabriela Skorupska (ORCID iD: 0000-0001-5828-2272) According to data released by WHO, at the beginning of 2021 there were Agnieszka Sujecka (ORCID iD: 0000-0002-0913-5273) 63 potential vaccines under clinical examinations, and over 172 in preclinical Klaudia Michalak (ORCID iD: 0000-0001-5001-7730) trials. The most promising vaccines are mRNA-based: Comirnaty (Pfizer- Agata Rojek (ORCID iD: 0000-0002-1450-0861) BioNTech), COVID-19 Vaccine (Moderna/NIAID) and CVnCoV (CureVac); vector Adrianna Bakowicz (ORCID iD: 0000-0002-9973-2935) vaccines: COVID-19 Vaccine (AstraZeneca/Oxford University), Gam-COVID- Weronika Kowalczyk (ORCID iD: 0000-0002-9080-4461) Vac (Gamaleja Institute, Russia) and JNJ-78436735/Ad.26.COV2.S. (Johnson Aleksandra Wojciechowska & Johnson), and NVX-CoV2373 recombinant subunit vaccine (Novavax). The (ORCID iD: 0000-0002-2489-7823) following groups of drugs potentially may be used in the COVID-19 therapy: Wiktoria Bęczkowska antiviral drugs with different mechanisms of action - blocking the binding of (ORCID iD: 0000-0002-4324-7607) SARS-CoV-2 to its specific receptor on cell membrane (angiotensin coverting Patryk Maj (ORCID iD: 0000-0002-2388-6698) enzyme 2; ACE2) and inhibiting viral entry into host cells (umifenovir, chloroquine, hydroxychloroquine, camostat mesylate and nafamostat); drugs Copyright that inhibit viral replication (inhibitors of RNA-dependent RNA polymerase, © Polskie Towarzystwo Farmaceutyczne e.g. remdesivir, favipiravir, ribovirin and molnupiravir; protease inhibitors, e.g. Kaletra); immunomodulating drugs (humanized monoclonal anti- To jest artykuł o otwartym dostępie, cytokine antibodies, e.g. adalimumab, infliximab, tocilizumab and anakinra; na licencji CC BY NC https://creativecommons.org/licenses/by-nc/4.0/ 178 Tom 77 · nr 2 · 2021 TERAPIA I LEKI andemia COVID-19, wywołana przez wirusa PSARS-CoV-2, od ponad roku szerzy się w róż- JAK kinase inhibitors – ruxolitinib and baricitinib), anti-inflammatory drugs nych stronach świata i stanowi poważne zagrożenie (glucocorticosteroids), and neutralizing monoclonal antibodies targeting the dla zdrowia publicznego. Liczne badania pozwo- SARS-CoV-2 spike protein (S). Moreover, low molecular weight heparin is liły na poznanie genomu, budowy i cyklu replika- used for prophylactic and therapeutic purposes. cji wirusa oraz odpowiedzi immunologicznej na zakażenie. Stanowią one podstawę do opracowania Keywords: COVID-19, SARS-CoV-2, vaccines, antiviral drugs, strategii mających na celu zapobieżenie dalszemu anti-cytokine monoclonal antibodies, JAK inhibitors, neutralizing rozprzestrzenianiu się COVID-19, a także zsyntety- monoclonal antibodies, glucocorticosteroids, heparin. zowanie i wprowadzenie do lecznictwa skutecznych oraz bezpiecznych szczepionek i leków. © Farm Pol, 2021, 77(2): 178–192 Do zapobiegania kolejnym zakażeniom i opano- wania pandemii COVID-19 nie wystarczy przestrze- ganie zasad sanitarnych (zachowanie dystansu spo- ochronie przed patogenami. Odporność wrodzona łecznego, stosowanie masek ochronnych oraz mycie odpowiada za wczesną reakcję obronną, umoż- rąk), potrzebne są przede wszystkim szczepionki. liwiającą detekcję i zwalczenie wirusów w ciągu Wg standardów WHO skuteczność szczepionek, kilku godzin. W humoralnej odporności wrodzo- które pozwoliłyby na uzyskanie odporności popu- nej główną rolę odgrywają: układ dopełniacza, lacyjnej, powinna wynosić co najmniej 50% [1]. peptydy o aktywności przeciwdrobnoustrojowej, Ze względu na podobieństwo budowy białka ostrej fazy i immunoglobuliny. W komór- powierzchniowego białka kolców (S) różnych pato- kowych mechanizmach obrony wrodzonej uczest- gennych szczepów wirusów z rodziny Coronavi- niczą głównie neutrofile, monocyty i makro- ridae istnieje prawdopodobieństwo, że przebycie fagi, komórki NK, komórki limfoidalne, komórki infekcji wywołanej przez jeden szczep może w pew- tuczne i komórki dendrytyczne. Odpowiedź ze nym stopniu chronić przed zakażeniem wirusem strony układu odporności swoistej pojawia się po SARS-CoV-2 lub ciężkim przebiegiem COVID-19. dłuższym czasie, natomiast może ona utrzymy- Powyższą hipotezę potwierdzają wyniki badań dia- wać się miesiącami bądź latami. Komórki pamięci gnostycznych – we krwi niektórych osób nieza- i przeciwciała, które są precyzyjnie skierowane infekowanych SARS-CoV-2 stwierdzono obecność przeciwko antygenom wirusa, pozwalają na szyb- limfocytów pomocniczych T zdolnych do wywoła- kie wykrycie i neutralizację czynnika zakaźnego. nia odpowiedzi immunologicznej przeciwko temu W powstawaniu odporności swoistej uczestniczą wirusowi [2]. Należy jednakże podkreślić, że prze- limfocyty T i B, przeciwciała i cytokiny [6]. bycie infekcji spowodowanej ludzkimi koronawi- Szczepionki uważane są za najbardziej bez- rusami nie gwarantuje długiego utrzymywania się pieczną formę ochrony pacjentów przed COVID-19, przeciwciał i możliwa jest reinfekcja [3]. Przeciwciała ponieważ działają poprzez modulowanie odpowie- IgG u osób, które wyzdrowiały po zakażeniu wiru- dzi układu odpornościowego. Szczepionki naśla- sem SARS-CoV zanikały po upływie około 2 lat [2]. dują kontakt z prawdziwym czynnikiem infekcyj- Opracowanie szczepionki to długotrwały i wielo- nym, aktywują limfocyty B i produkcję przeciwciał. etapowy proces. Od rozpoczęcia badań do wprowa- Wytwarzana jest pamięć immunologiczna w celu dzenia szczepionki na rynek upływa zazwyczaj od skutecznego zwalczenia patogenu w przypadku 10 do 15 lat. W bezprecedensowej pandemii COVID- powtórnego kontaktu [7]. 19 podejmowane są wspólne wysiłki wielu ośrod- Idealna szczepionka do walki z pandemią ków w celu przyspieszenia przedklinicznej i kli- COVID-19 powinna posiadać następujące cechy [8]: nicznej oceny potencjalnych szczepionek, a także - wywołać długotrwałą ochronną odpowiedź uzyskania akceptacji przez odpowiednie organy immunologiczną; [2]. Według danych WHO, na początku stycznia - może być stosowana bez względu na chorobę 2021 r. w fazie badań klinicznych były 63 szcze- współistniejącą lub wiek, stan odporności, pionki, a ponad 172 w badaniach przedklinicz- ciążę/karmienie piersią; nych [4]. W grudniu 2020 r., po upływie około roku - nie może wywoływać wzmocnienia zależnego od wykrycia pierwszego przypadku infekcji wiru- od przeciwciał lub patologicznych zmian w płu- sem SARS-CoV-2 u człowieka, pojawiły się pierw- cach o podłożu immunologicznym; sze dostępne szczepionki przeciwko COVID-19 [5]. - powinna być termostabilna, aby umożliwić Układ odpornościowy obejmuje odpor- transport i przechowywanie w krajach rozwi- ność wrodzoną (nieswoistą) i nabytą (swoistą); jających się; dzielą się one na odpowiedź humoralną i komór- - powinna być wysoce immunogenna (wzbudzać kową. Współdziałanie obu podstawowych typów nabytą odpowiedź immunologiczną) w popu- odporności odgrywa kluczową rolę w skutecznej lacji ogólnej, w tym w populacji z wcześniej Tom 77 · nr 2 · 2021 179 TERAPIA I LEKI istniejącymi przeciwciałami przeciw wekto- wirionu, co zapewnia utrzymanie zdolności anty- rom wirusowym wykorzystanym do produk- genu do wytworzenia odpowiedzi immunologicz- cji szczepionki. nej. Teoretycznie szczepionki inaktywowane są Za główny cel dla przeciwciał neutralizujących łatwe do wytworzenia i antygenowo podobne do i uzyskania odpowiedzi immunologicznej ze strony patogennych wirusów [10]. Tego typu szczepionki limfocytów T obrano powierzchniowe glikoprote- można stosować z adjuwantami (np. wodorotlen- iny kolców (S) wirusa. Szczepionki oparte na białku kiem glinu, fosforanem glinu, CpG1018, Matrix-M1, S mają za zadanie pobudzać tworzenie
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