Coronavirus Disease Research Community - COVID-19
Published January 23, 2021 | Version v1
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mRNA Based Vaccine Studies in Infectious Diseases and Current Developments

Creators

  • 1. Department of Infectious Disease, Gulhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey

Description

Özet

Başlangıçta genetik hastalıkların tedavisinde in-vivo protein ekspresyonu için geliştirilen mRNA teknolojisi, terapötik kanser aşıları yönüne doğru gelişirken, bu aşıların tolere edilebilirliği ve immünojenisitesi ile ilgili ilk veriler bu yeni platformun geleneksel aşı yaklaşımlarının yetersiz kaldığı enfeksiyonlar için koruyucu bağışıklık geliştirilmesinde yeni bir alternatif sistem olabileceği fikrini ortaya çıkarmıştır. mRNA teknolojisi influenza virus, RSV (Respiratory syncytial virus), HIV (Human immunodeficiency virus), CMV (human cytomegalovirus), kuduz, MMLV (moloney murine leukaemia virus), Ebolavirus, insan papilloma virus (HPV), Zika virus, hepatit C virusu (HCV) ve Kırım Kongo Kanamalı Ateş Virusu (KKKAV) gibi farklı virüsler yanında, Streptococcus türü bakteriler ve Toxoplasma gondii gibi paraziter enfeksiyonlara yönelik koruyucu aşı geliştirme çalışmalarında son yıllarda denenen umut verici yeni bir yaklaşım olmuştur. mRNA aşılarının neredeyse standartlaştırılabilir bir platform üzerinde hızlı aşı tasarımına imkan vermesi yanında, ölçeklenebilir üretim kapasitesi bu aşıları yeni ortaya çıkan salgınların kontrol altına alınması ve önlenmesi için bir umut haline getirmiştir. SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) pandemisinde bu özelliği ile öne çıkan mRNA aşıları birçok gelişmiş ülkeden milyarlarca doz aşı talebi almış ve 2020 yılı sonlarından itibaren acil kullanım onayları ile milyonlarca kişiye uygulanmıştır. Replike olabilen mRNA aşı formatlarının çok daha düşük aşı dozlarında bağışık yanıtı uyarabilmesi, dolayısıyla düşük maliyetli erişim imkanı sunması ve mRNA aşılarının konak genomuna entegre olma riski taşımayıp geçici ve kontrol edilebilir bir antijenik uyarı yapması bu yeni aşıların diğer avantajlarıdır. Aşıların zayıf stabilitesi, immünojenisitelerinin dengelenmesi, bazı aşılarda soğuk zincir koşullarında dağıtım gereksinimi, bazı enfeksiyöz etkenler için istenilen düzeyde koruyuculuk elde edilememesi ve uzun dönem yan etkileri ile ilgili verilerin sınırlı olması gibi halen çözüm bekleyen veya geliştirilmesi gereken bazı zorluklar da bulunmaktadır. Kapsamlı klinik çalışmaların sonuçları ile elde edilecek güvenlik kanıtlarından sonra yeni teknik gelişmelerin de katkısı ile mRNA temelli aşıların gelecekte daha yaygın olarak kullanılması beklenmektedir. Bu makalede enfeksiyon hastalıklarına yönelik geliştirilen profilaktik mRNA aşı çalışmalarından elde edilen sonuçların kısa bir özeti sunulmuştur.

Abstract

While mRNA technology, which was originally developed for in-vivo protein expression in the treatment of genetic diseases, is developing towards therapeutic cancer vaccines, initial data on the tolerability and immunogenicity of these vaccines led to the idea that this new platform could be a new alternative system for developing protective immunity for infections where conventional vaccine approaches fall short. mRNA technology has been a promising new approach that has been tried in recent years in preventive vaccine development researches for different viruses such as influenza virus, RSV (Respiratory syncytial virus), HIV (Human immunodeficiency virus), CMV (human cytomegalovirus), rabies virus, MMLV (moloney murine leukemia virus), Ebolavirus, human papilloma virus (HPV), Zika virus, hepatitis C virus (HCV ) and Crimean Congo Hemorrhagic Fever Virus (CCHFV), as well as bacterial and parasitic infections such as Streptococcus spp. and Toxoplasma gondii. mRNA vaccines allow rapid vaccine design on a practically standardizable platform, in addition, scalable production capacity has become these vaccines a hope for containment and prevention of emerging epidemics. In the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) pandemic, mRNA vaccines, which stand out with this feature, have received billions of doses of vaccine requests from many developed countries and have been applied with emergency use approvals since the end of 2020 to millions of people. Other advantages of these new vaccines are that replicable mRNA vaccine formats can induce an immune response at much lower vaccine doses, thus offering low-cost access, and that mRNA vaccines do not have the risk of integrating into the host genome and provide a temporary and controllable antigenic stimulation. There are also some challenges that still need to be resolved or need to be developed, such as the weak stability of vaccines, balancing their immunogenicity, the need for distribution in cold chain conditions for some vaccines, the inability to achieve the desired protection levels for some infectious agents and limited data on long-term side effects. After the safety evidence to be obtained with the results of extensive clinical studies, it is expected that mRNA-based vaccines will be used more widely in the future with the contribution of new technical developments. A summary of the results of the prophylactic mRNA vaccine studies that are being developed for infectious diseases is provided in this article.

Notes

Enfeksiyon Hastalıklarında mRNA Temelli Aşı Çalışmaları ve Güncel Gelişmeler

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