Iintsholongwane ezintathu ze-adenovirus ezisetyenziswa njengee-vectors ukuvelisa izitofu zokugonya ze-COVID-19, zibophelela kwi-platelet factor 4 (PF4), iprotein ebandakanyeka kwi-pathogenesis yokuphazamiseka kwe-clotting.
I-Adenovirus esekwe kwi-COVID-19 zokugonya njenge Oxford/AstraZeneca's ChAdOx1 sebenzisa inguqulelo ebuthathaka kunye nokuguqulwa kofuzo lwengqele eqhelekileyo intsholongwane adenovirus (iDNA intsholongwane) njengeVector yokubonakalisa iprotein yentsholongwane yenoveli coronavirus nCoV-2019 emzimbeni womntu. Iprotheyini yentsholongwane echaziweyo iphinda isebenze njenge-antigen kuphuhliso lwe-immunity esebenzayo. I-adenovirus esetyenzisiweyo kukuphindaphinda intsingiselo engafanelekanga ukuba ayinakuphindaphinda emzimbeni womntu kodwa njenge-vector inika ithuba lokuguqulelwa kwe-gene encoding ye-Spike protein (S) yenoveli. intsholongwane ye-Corona1. Ezinye ii-vectors ezinjengabantu i-adenovirus uhlobo lwama-26 (HAdV-D26; esetyenziselwa isitofu sokugonya i-Janssen COVID), kunye nabantu i-adenovirus uhlobo 5 (HAdV-C5) nazo zisetyenziselwe ukuvelisa zokugonya ngokuchasene ne-SARS-CoV-2.
Isitofu sokugonya se-Oxford/AstraZeneca COVID-19 (ChAdOx1 nCoV-2019) sifunyenwe sisebenza kulingo lwezonyango kwaye samkelwa ngabalawuli kumazwe aliqela (sifumene imvume yi-MHRA e-UK nge-30 kaDisemba 2020). Ngokungafaniyo nolunye ugonyo lwe-COVID-19 (ugonyo lwe-mRNA) olukhoyo ngelo xesha, oku kwakucingelwa ukuba kunenzuzo enxulumene nokugcinwa kunye nolungiselelo. Kungekudala yaba sesona sitofu sokugonya kumlo ochasene nobhubhane kwihlabathi liphela kwaye yenza igalelo elibalulekileyo ekukhuseleni abantu kwihlabathi liphela kwi-COVID-19.
Nangona kunjalo, ikhonkco elinokubakho phakathi kogonyo lwe-AstraZeneca lwe-COVID-19 kunye nehlwili legazi larhanelwa xa malunga neemeko ezingama-37 zeziganeko ezinqabileyo zamahlwili egazi zaxelwa (ngaphandle kwezigidi ezili-17 zabantu abagonyiweyo) kwi-EU naseBritane. Ukukhanya kwesi siphumo sinokwenzeka, emva koko, iPfizer's okanye iModerna's mRNA Iigonya zacetyiswa2 ukuba isetyenziswe kwabo bangaphantsi kweminyaka engama-30. Kodwa kunqabile kangakanani ukuphazamiseka kwe-clotting njenge-thrombocytopenia syndrome (TTS), imeko efana ne-heparin-induced thrombocytopenia (HIT) ebonwa kubantu abalawulwa ngesitofu sokugonya se-AstraZeneca COVID-19 esebenzisa i-ChAdOx1 (itshimpanzi i-adenovirus Y25) i-vector ibangelwa kwaye indlela ephantsi echaphazelekayo, ihlala ingacacanga.
Uphononongo lwakutsha nje olupapashwe kwi-Science Advances ngu-Alexander T. Baker et al. ibonisa ukuba ezintathu adenoviruses zisetyenziswa njengeevektha ukuvelisa i-SARS-CoV-2 zokugonya, bophezela kwi-platelet factor 4 (PF4), iprotheni echaphazelekayo kwi-pathogenesis ye-HIT kunye ne-TTS.
Kusetyenziswa ubuchule obaziwa ngokuba yi-SPR (i-Surface Plasmon Resonance), kwaboniswa ukuba i-PF4 ayibophelelanga kuphela kulungiselelo lwe-vector olusulungekileyo lwezi vektha, kodwa kunye zokugonya evela kwezi vectors, kunye nobudlelwane obufanayo. Olu nxibelelwano lubangelwe kubukho besakhono esinamandla somphezulu we-electropositive kwi-PF4 enceda ekubopheleleni kumandla ombane owomeleleyo kwi-adenoviral vectors. Kwimeko yolawulo lwesitofu sokugonya se-ChAdOx1 covid, isitofu sokugonya esitofelwe kwisihlunu sinokuvuza kwigazi, okukhokelela ekusekweni kwe-ChAdOx1/PF4 eyinkimbinkimbi njengoko kuchaziwe ngasentla. Kwiimeko ezinqabileyo, umzimba uyayibona le nto inzima njengento yangaphandle intsholongwane kwaye ibangela ukwakheka kwee-PF4 antibodies. Ukukhululwa kwee-antibodies ze-PF4 kukhokelela ngakumbi ekudityanisweni kwe-PF4, ngaloo ndlela kuqulunqa amahlwili egazi, kukhokelela kwiingxaki ezingakumbi kwaye kwiimeko ezithile, ukufa kwesigulane. Ukuza kuthi ga ngoku oku kukhokelele ekuswelekeni kwabantu abangama-73 kumayeza okugonya aphantse abe zizigidi ezingama-50 ogonyo lwe-AstraZeneca olunikwe e-UK.
Isiphumo se-TTS esibonwayo sigqame kakhulu emva kwedosi yokuqala yesitofu sokugonya kunedosi yesibini, icebisa ukuba izilwa-buhlungu ezilwa ne-P4 zinokungahlali xesha lide. I-ChAdOx-1/PF4 complex ivinjwe ubukho be-heparin edlala indima ebalulekileyo kwi-HIT. I-Heparin ibophelela kwiikopi ezininzi zeprotheni ye-P4 kwaye yenze i-aggregates kunye ne-anti-P4 antibodies evuselela ukusebenza kweplatelet kwaye ekugqibeleni iholele kwi-blood clots.
Ezi ziganeko zinqabileyo ezibeka ubomi esichengeni zibonisa ukuba kukho imfuneko yobunjineli iintsholongwane ngendlela enje, ukuze kuthintelwe nakuphi na ukusebenzisana neeproteni zeselula ezinokukhokelela kwii-SARs (Iimpendulo eziMandundu eziMandundu), nto leyo ekhokelela ekufeni komguli. Ngapha koko, umntu unokujonga ezinye iindlela zokuyila zokugonya isekelwe kwiprotheyini engaphantsi kweeyunithi kune-DNA.
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Imithombo:
- Isitofu sokugonya se-Oxford/AstraZeneca COVID-19 (ChAdOx1 nCoV-2019) Sifunyaniswe sisebenza kwaye samkelwe. Inzululwazi yaseYurophu. Ipapashwe nge-30 kaDisemba 2020. Ifumaneka apha https://www.scientificeuropean.co.uk/covid-19/oxford-astrazeneca-covid-19-vaccine-chadox1-ncov-2019-found-effective-and-approved/
- Soni R. 2021. Unxulumano olunokwenzeka phakathi kwe-AstraZeneca ye-COVID-19 yokugonya kunye namahlwili egazi: Ngaphantsi kweminyaka engama-30 iza kunikwa i-Pfizer's okanye iModerna's mRNA Vaccine. Inzululwazi yaseYurophu. Ipapashwe nge-7 kuTshazimpuzi 2021. Ifumaneka e https://www.scientificeuropean.co.uk/covid-19/possible-link-between-astrazenecas-covid-19-vaccine-and-blood-clots-under-30s-to-be-given-pfizers-or-modernas-mrna-vaccine/
- Baker AT, okqhubekayo 2021. I-ChAdOx1 isebenzisana ne-CAR kunye ne-PF4 kunye nemiphumo ye-thrombosis kunye ne-thrombocytopenia syndrome. Ukuqhubela phambili kwezeNzululwazi. Umqulu 7, ushicilelo 49. Ipapashwe nge-1 kaDec 2021. DOI: https//doi.org/10.1126/sciadv.abl8213
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