Literaturni pregled kliničnega vrednotenja vektorskih cepiv proti infekcijskim boleznim

Gracar, Klavdija (author), Bratkovič, Tomaž (mentor)

Cepiva so profilaktična zdravila, s katerimi izzovemo imunski spomin proti specifičnim antigenom patogenov in s tem zaščito pred določeno infekcijsko boleznijo. Razmeroma nova skupina cepiv so t.i. vektorska cepiva. Njihova posebnost je dostava genskega zapisa za cepilni antigen v telesne celice s prenašalno (vektorsko) DNA, bodisi s plazmidom ali s (praviloma) replikacijsko onesposobljenim virusnim vektorjem. Vektorskih cepiv z dovoljenjem za promet še ni veliko. Po svetu sta tržno dovoljenje dobili dve virusni vektorski cepivi proti flavivirusom (virusu japonskega encefalitisa in virusu denga), pet virusnih vektorskih cepiv proti virusu ebole (tri imajo dovoljenje za promet v EU: Ervebo, Zabdeno in Mvabea) ter štiri virusna vektorska cepiva proti virusu SARS-CoV-2 (v EU je odobrena le uporaba cepiv Vaxzevria in Jcovden). Zgolj v Indiji ima dovoljenje za promet vektorsko cepivo na osnovi plazmidne DNA proti virusu SARS-CoV-2 (ZyCov-D). V magistrski nalogi predstavljamo podatke o kliničnih raziskavah zgoraj navedenih cepiv. Za vsako predstavljeno raziskavo smo opisali celotno shemo raziskave (vrsta raziskave, število udeležencev, jakost in število prejetih odmerkov), seveda pa tudi same rezultate raziskave (zaznani neželeni učinki in njihova pogostost, imunogenost ter učinkovitost cepiva). Pri vsem tem smo se naslanjali na znanstvene članke, ki smo jih poiskali v zbirkah PubMed, medRxiv in bioRxiv, prav tako pa smo podatke pridobili tudi iz uradnih spletnih strani regulatornih organov (EMA, FDA, CDC, WHO, JAZMP). Rezultati raziskav so pokazali, da so udeleženci vektorska cepiva dobro prenašali in da so le-ta varna. Neželeni učinki so bili pri vseh vektorskih cepivih blagi do zmerni s trajanjem do nekaj dni, najpogosteje pa so se pojavile bolečine na mestu injiciranja, bolečine v mišicah in sklepih, povišana telesna temperatura, glavobol in utrujenost. Posebni resni neželeni učinki se niso pojavili, ali pa so se pojavili zelo redko, vendar v večini primerov niso bili povezani s cepivom. Posebno pozornost pa so vendarle namenili sindromoma tromboze s trombocitopenijo in kapilarnega prepuščanja, ki sta se v zelo redkih primerih pojavila po cepljenju s cepivoma Jcovden in Vaxzevria. Vektorska cepiva so se izkazala tudi za zelo imunogena in učinkovita. Protitelesa je namreč razvilo več kot 90 % udeležencev pri vsakem od cepiv. Za najbolj učinkovito se je izkazalo virusno vektorsko cepivo Sputnik V, katerega učinkovitost je bila kar 91,6 %, najmanj učinkovito pa je bilo cepivo Convidecia, in sicer 63,7 %. Vsa ostala cepiva so izkazovala zelo podobno učinkovitost (70 % - 75 %). Kljub obetavnim rezultatom, ki so jih pokazale klinične raziskave, prihodnost vektorskih cepiv ogrožajo sicer izjemno redki, a hudi in še ne ustrezno pojasnjeni resni neželeni učinki.

• Language: Slovenian
• Keywords: vektorska cepiva, klinične raziskave, varnost, učinkovitost, ebolavirus, SARS-CoV-2
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-147033
• Publication date in RUL: 21.06.2023

Secondary language

• Language: English
• Title: Clinical trials of vector vaccines against infectious diseases: a literature review

Abstract

Vaccines are prophylactic drugs used to induce immune memory against specific antigens of pathogens, thereby providing protection against a certain infectious disease. Vector vaccines constitute a relatively new group of vaccines, based on a DNA vehicle (the so-called vector, i.e., either a plasmid or (typically) a replication-defficient viral vector) to deliver genetic information for the vaccine antigen to somatic cells. There are only a few marketed vector vaccines world-wide: two against flaviviruses (Japanese encephalitis and dengue), five against Ebola (three of which (Ervebo, Zabdena and Mvabea) are approved in the EU) and four against the SARS-CoV-2 virus (with Vaxzevria and Jcovden approved in the EU. A single vector vaccine based on a plasmid DNA (ZyCov-D) against the SARS-CoV-2 virus has been authorized in India. In the present thesis, we present data on clinical trials of the above-mentioned vaccines. We describe the research schemes (type of trial, number of participants, strength and number of doses received), as well as the results of the trials (perceived adverse effects and their frequency, immunogenicity and effectiveness of the vaccine). We collected data from scientific papers, searching in PubMed, medRxiv and bioRxiv databases, as well as from the official websites of the regulatory authorities (EMA, FDA, CDC, WHO, JAZMP). In general, vector vaccines were well tolerated by the trial participants and were safe. Adverse effects were largely mild to moderate for all vector vaccines, lasting up to a few days. The most common were pain at the injection site, muscle and joint pain, fever, headache, and fatigue. Serious adverse effects did not occur, or occurred very rarely during clinical trials, but in most cases were not related to the vaccine. However, special attention was paid to the syndromes of thrombosis with thrombocytopenia and capillary leak, which appeared in very rare instances after vaccination with the Jcovden and Vaxzevria vaccines. Vector vaccines have also been shown to be highly immunogenic and effective. More than 90 % of the participants developed antibodies to each of the vaccines. The viral vector vaccine Sputnik V proved to be the most effective, the effectiveness of which was as much as 91,6 %, while the least effective was the Convidecia vaccine, the effectiveness of which was 63,7 %. All other vaccines had very similar effectiveness (70 % - 75 %). Despite the promising results of clinical trials, the future of vector vaccines is threatened by extremely rare but very severe and not yet adequately explained serious adverse effects.

• Keywords: vector vaccines, clinical trials, safety, efficacy, ebolavirus, SARS-CoV-2