Četiri decenije profilaktičkog istraživanja EBV vakcine: sistematski pregled i istorijska perspektiva.
Frontiers in immunology
Sažetak istraživanja
Pozadina Epstein-Barr virus (EBV) je uzročnik infektivne mononukleoze i povezan je s raznim vrstama raka i autoimunim bolestima. Uprkos decenijama istraživačkih napora u borbi protiv ovog velikog globalnog zdravstvenog opterećenja, ne postoji odobrena profilaktička vakcina protiv EBV-a. Kako bismo olakšali racionalan dizajn i procjenu efikasne vakcine, sistematski smo pregledali pretkliničke i kliničke profilaktičke studije EBV vakcine kako bismo odredili antigene, platforme za isporuku i životinjske modele korištene u ovim studijama.
Metode Pretraživali smo Cochrane biblioteku, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO Global Index Medicus i Google Scholar od početka do 20. juna 2020. za studije profilaktičke vakcine protiv EBV-a fokusirane na humoralni imunitet.
Rezultati Pretraga je dala 5.614 jedinstvenih studija. 36 pretkliničkih i 4 kliničke studije uključene su u analizu nakon skrininga prema kriterijima isključenja. U pretkliničkim studijama, gp350 je bio najčešće korišten imunogen (33 studije), vakcine su najčešće isporučene kao monomerni proteini (12 studija), a miševi su bili najčešće korišteni životinjski model za testiranje imunogenosti (15 studija). Prema adaptaciji kontrolne liste CAMARADES, 4 pretkliničke studije su ocijenjene kao vrlo visoke, 5 kao visoke, 13 kao umjerene kvalitete, 11 kao loše i 3 kao vrlo loše. U kliničkim studijama, gp350 je bio jedini antigen vakcine, isporučen na platformi vakcinije (1 studija) ili kao monomerni protein (3 studije). Ova studija je registrovana u PROSPERO (CRD42020198440).
Zaključci Četiri glavne prepreke spriječile su razvoj efikasne profilaktičke EBV vakcine: nedefinisani korelati imunološke zaštite, nedostatak znanja o idealnim EBV antigenima za vakcinaciju, nedostatak odgovarajućeg životinjskog modela za testiranje efikasnosti vakcine i nedostatak znanja o idealnoj platformi za isporuku vakcine. Naša analiza podržava multivalentni antigenski pristup koji uključuje dva ili više od pet glavnih glikoproteina uključenih u ulazak virusa (gp350, gB, gH/gL, gp42) i multimerni pristup za predstavljanje ovih antigena. Očekujemo da će primjena dva nedovoljno korištena modela izazova, rezus makakija osjetljivog na rhesus limfokriptovirus (homolog EBV) i običnih marmozeta, omogućiti uspostavljanje in vivo korelata imunološke zaštite i dobivanje podataka koji se mogu generalizirati. Registracija sistematskog pregleda https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifikator PROSPERO I.D. CRD4202019844.
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Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective.
Background Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.
Methods We searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.
Results The search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).
Conclusions Four major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of in vivo correlates of immune protection and attainment of more generalizable data. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
Izvorni podaci
- DOI
- 10.3389/fimmu.2022.867918
- PMID
- 35493498
- PMCID
- PMC9047024
- Provjereno
- 2026-07-26
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