Review of COVID-19 mRNA Vaccines: BNT162b2 and mRNA-1273

Abstract

The United States Food and Drug Administration recently issued emergency use authorization for 2 mRNA vaccines for preventing COVID-19 disease caused by SARS-CoV-2 virus infections. BNT162b2 from Pfizer-BioNTech and mRNA-1273 by Moderna are planned for use in mass-immunization programs to curb the pandemic. A brief overview of COVID-19 mRNA vaccines is provided, describing the SARS-CoV-2 RNA, how mRNA vaccines work and the advantages of mRNA over other vaccine platforms. The Pfizer-BioNTech collaboration journey to short-list mRNA vaccine candidates and finally selecting BNT162b2 based on safety data is outlined, followed by the Phase 3 study of BNT162b2 demonstrating 95% efficacy in preventing COVID-19 infections. Studies regarding mRNA-1273 (Moderna) are described, including extended immunogenicity data up to 119 days. The Phase 3 COVE study of mRNA-1273 eventually showed vaccine efficacy of 94.5%. Recommendations for future mRNA vaccine development are provided, including ongoing safety surveillance, evaluation in under-represented groups in previous studies and improving mRNA vaccine thermostability. Finally, further logistical considerations are required for manufacturing, storing, distribution and implementing mass vaccination programs to curb the pandemic.

“An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity That Limit Response to Non-Pathogens”

“…The COVID-19 pandemic revealed the remarkable vulnerability of older people exposed to emerging infections, with rates of death in the elderly several hundred-fold greater than in the young. It is heartening that the Pfizer-BioNTech and Moderna mRNA vaccines can effectively induce protective responses even in aged individuals (Anderson et al, 2020;Teo, 2021). We speculate that the mRNAlipid nanoparticle vaccine platform provides the surrogates of pathogen infection that we believe are necessary for strong activation of even the aged immune system (Pardi and Weissman, 2020).…”

A Yellow Fever 17D Virus Replicon-Based Vaccine Platform for Emerging Coronaviruses

“…The current SARS-CoV-2 pandemic is showcasing the importance that novel platforms can have for the fast development of antiviral vaccines against emerging viruses that threaten global populations, and in particular, the need for versatile platforms from which safe and effective vaccines can readily be derived. The undeniable success of the novel mRNA-based vaccines produced by Biontec/Pfizer and Moderna [62] has opened important perspectives for innovative vaccine approaches in general. The adenovirus-based vaccine platforms used by AstraZeneca and Janssen Vaccines and Therapeutics and their academic partners are also considered safe and efficacious by the European Medicines Agency [63,64].…”

Nanotechnologies in Delivery of DNA and mRNA Vaccines to the Nasal and Pulmonary Mucosa

“…First, IVT-mRNA can be modified with a Cap 0 (m7GpppN) structure using VCE. Then, using 2 O-methyltransferase, Cap 0 can be switched to Cap 1 (m7GpppmN), which enhances the translation efficiency of IVT-mRNA [161,162]. However, large-scale manufacturing of IVT-mRNA may consume a huge amount of enzymes using this approach, which would increase the production costs and limit the approach's widespread application [5].…”

“…Recently, CleanCap ® , a method developed by TriLink Biotechnology, was reported to generate IVT-mRNA with high translational efficiency, simplifying the production of 5 -capped IVT-mRNA. Based on these advantages, the approach of CleanCap ® has been used for 5 capping of BNT162b2 and mRNA-1273 vaccines [161,172].…”