SARS-CoV-2’YE KARŞI GELİŞTİRİLEN AŞILAR VE ÜRETİM METOTLARI

Year 2021, Volume: 4 Issue: 2, 14 - 32, 31.08.2021

Beyza Şerefoğlu , Rabia Çakır Koç , Begüm Kübra Tokyay , Gizem Yolalan , Berrak Gülçin Balaban , Yigit Tanyeri , Sezer İslambey

Abstract

Yeni koronavirüs (SARS-CoV-2) virüsünün sebep olduğu Covid-19 pandemisi dünya genelinde 4,3 milyon kişinin ölümüne ve 203 milyon kişinin hastalanmasına sebep olmuştur. Yeni tanımlanan bu virüs, hızlı yayılması ve ciddi hasarlar bırakması sebebiyle hastaneye yatış oranlarını arttırmıştır. Toplum sağlığı ve ülke ekonomileri olumsuz etkilenmiştir. Pandemiyi sonlandırmanın en etkili yolu aşı geliştirilmesi ve etkin aşılamanın yapılmasıdır. Tüm dünyada ve ülkemizde Covid-19’a yönelik aşı geliştirme çalışmaları yapılmaktadır.
Geleneksel bir aşı türü olan inaktif aşılar, uzun yıllar çalışılmış, yan etkileri bilinen, güvenilir aşılardır. İnaktive edilen virüsün immün yanıt oluşturması esasına dayanır. Üretim metodu; virüsün izole edilmesi, hücre kültüründe çoğaltılması, inaktivasyonu ve saflaştırılmasının ve genellikle bir adjuvan ile formülize edilmesidir. Rekombinant protein aşıları, rekombinant DNA teknolojisi ile virüsün viral proteinlerini sentezlemektedir. Üretiminde, SARS-CoV-2 viral proteinlerini kodlayan gen bölgelerinin uygun plazmidler aracılığı ile seçilen in vivo ortamda ekspresyonu, saflaştırılması ve adjuvan ile formülizasyonu yer alır. Virüs benzeri yapılar (VLP) ile oluşturulan aşılar, virüsü taklit ederek antijenik yapıyı tanıtırlar. Üretimlerinde çeşitli konakçı sistemler kullanıldığından, saflaştırma basamakları değişmektedir. Adenovirüs aşılarında viral vektör aracılığı ile immün yanıt oluşturması hedeflenmektedir. Üretiminde antijen kodlayan gen genellikle adenovirüse entegre edilir ve konakçı hücrelerde çoğaltıldıktan sonra hücreler parçalanarak saflaştırılır ve formülize edilir. Sentetik peptit aşıları, patojenin immünojenik bölgesini peptitler ile taklit eden aminoasit dizilerinden oluşur. Aşının üretimi; peptit sentezi, taşıyıcı protein konjugasyonu ve adjuvanlama/formülasyon aşamalarını içerir. mRNA aşılarında ise amaç, viral proteinin insan hücresinde in vivo ekspresyonunu sağlamaktır. Üretimde, mRNA dizilerini içeren plazmidler ile sentezlenen mRNA’ların saflaştırılması ve lipit nanopartiküller ile formülize edilmesini içerir. Bu derlemede, Covid-19’a yönelik geliştirilen aşıların teknolojileri ve üretim metotları avantaj ve dezavantajları ile birlikte değerlendirilmiştir.

Keywords

Covid-19, Aşı, Üretim, İnaktif, Rekombinant, mRNA, Vektör

Supporting Institution

Türkiye Sağlık Enstitüleri Başkanlığı

Project Number

11548NL

Thanks

Türkiye Sağlık Enstitüleri Başkanlığı (TÜSEB) tarafından desteklenen 11548NL numaralı, “SARSCOV-2 Virüsüne Karşı İnaktif Virüs Aşısı ile Rekombinant Aşısı Üretimi için Preklinik Sonrası Proses Geliştirilmesi” başlıklı proje kapsamında hazırlanan derlemede kuruma destekleri için teşekkür ederiz.

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