Analiza učinka mRNA BNT162b cjepiva na angiogene čimbenike PlGF i sFlt-1

master's thesis

• Title (english): Analysis of mRNA BNT162B vaccine effect on angiogenic factors PlGF and sFlt-1
• Author: Tamara Matić
• Mentor: Anita Somborac Bačura (mentor)
• Mentor: Domagoj Marijančević (mentor)
• Committee member: Anita Somborac Bačura (predsjednik povjerenstva)
• Committee member: Sandra Šupraha-Goreta (član povjerenstva)
• Committee member: Domagoj Marijančević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2023-06-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Pojava tromboembolijskih incidenata s početkom procjepljivanja protiv SARS-CoV-2 zasigurno je jedna od najvećih dilema koju je donijela pandemija Covid-19. Vodeći se činjenicom da cijepljenje oponaša prirodnu infekciju, pretpostavljeno je da uslijed poremećene regulacije renin-angiotenzin sustava vezanjem šiljastog proteina može doći do angiogene neravnoteže te hiperkolagulabilnog stanja koje je u pozadini tromboemboliskih incidenata. U skladu s tim, ovim istraživanjem ispitivan je učinak mRNA BNT162b cjepiva na koncentracije angiogenih čimbenika PlGF i sFlt-1. Konkretni ciljevi bili su ispitati utjecaj cijepljenja na koncentracije PlGF i sFlt-1, razliku u koncentracijama između podskupina ispitanika bez hipertenzije i s hipertenzijom, te povezanost PlGF i sFlt-1 s dobi te indeksom tjelesne mase u pojedinim vremenskim točkama nakon cijepljenja. Predmet ovog istraživanja bila su 33 odrasla ispitanika cijepljena mRNA BNT162b cjepivom. Koncentracije čimbenika mjerene su istovjetno u 5 vremenskih točaka: T0 – točka mjerenja neposredno prije 1. doze (unutar 24h); T1 – točka mjerenja 7 dana nakon 1. doze; T2 – točka mjerenja 14 dana nakon 1. doze; T3 – točka mjerenja 7 dana nakon 2. doze; T4 – točka mjerenja 14 dana nakon 2. doze. Za laboratorijsku analizu je korištena elektrokemiluminiscentna imunokemijska metoda (ECLIA) temeljena na sendvič principu. Statistički značajna razlika između određivanih koncentracija kod svh ispitanika procijenjena je Wilcoxon signed-rank testom, dok je statistički značajna razlika između određivanja kod ispitanika bez hipertenzije i s hipertenzijom ispitana Mann-Whitneyevim testom. Moguća povezanost čimbenika s dobi te indeksom tjelesne mase ispitana je Spearmanovom korelacijom. Detaljnom analizom, unatoč određenim statistički značajnim razlikama, nisu pronađene klinički značajne promjene u koncentracijama PlGF i sFlt-1 uvjetovane cijepljenjem, niti je utvrđena razlika u koncentracijama između podskupina ispitanika bez hipertenzije i s hipertenzijom. Također, nije utvrđena značajna povezanost koncentracija PlGF i sFlt-1 u pojedinim točkama nakon cijepljenja s dobi, niti s indeksom tjelesne mase. S obzirom na dobivene rezultate, nije dokazano da pretpostavljeni mehanizam ima ulogu u nastanku tromboembolijskih incidenata nakon cijepljenja mRNA BNT162b cjepivom.

Abstract (english)

The incidence of thromboembolic events after SARS-CoV-2 vaccination is still one of the biggest concerns of the Covid-19 pandemic. Since vaccination imitates natural infection, we hypothesized that the dysregulation of the renin-angiotensin system, caused by spike protein binding, could induce an angiogenic imbalance leading to a hypercoagulable state and thromboembolic events. Based on this hypothesis, we tested dynamics in angiogenic factor concentration changes caused by the mRNA BNT162b vaccine. The specific aims of this study were to test the effect of vaccination on PlGF and sFlt-1 concentrations, the concentration difference between subgroups without and with hypertension, and to examine the correlation between PlGF and sFlt-1 with age and body mass index at defined time points after vaccination. The study included 33 adult subjects who were vaccinated with the mRNA BNT162b vaccine. Factors' concentrations were measured at five time points: T0 – measurement point before the1st dose (within 24h); T1 – measurement point 7 days after the 1st dose; T2 – measurement point 14 days after the 1st dose; T3 – measurement point 7 days after the 2nd dose; T4 – measurement point 14 days after the 2nd dose. Factors were measured using electrochemiluminescence method (ECLIA) based on the sandwich principle. The statistically significant difference between the measurements for all subjects was tested using Wilcoxon signed-rank test, while the statistically significant difference between subjects without and with hypertension was tested by using Mann-Whitney test. The possible correlation was tested by Spearman's correlation. Although statistically significant differences were obtained, they are indicated to be clinically irrelevant. No clinically significant changes in PlGF and sFlt-1 concentrations were found after vaccination. There were no differences in concentrations between subjects without hypertension and those with hypertension. No correlation was found between PlGF and sFlt-1 concentrations with age or body mass index at any time point after vaccination. According to the results, it has not been proven that the assumed mechanism participates in the incidence of thromboembolic incidents after vaccination with the mRNA BNT162b vaccine.

• Keywords: COVID-19; SARS-CoV-2; cjepivo; mRNA BNT162b; PlGF; sFlt-1
• Keywords (english): COVID-19; SARS-CoV-2; vaccine; mRNA BNT162b; PlGF; sFlt-1
• Language: croatian
• URN:NBN: urn:nbn:hr:163:579138
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-06-27
• Created on: 2023-12-07 13:22:10