Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

Abstract

In December 2019, a new and highly pathogenic coronavirus emerged—coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), quickly spread throughout the world. In response to this global pandemic, a few vaccines were allowed for emergency use, beginning in November 2020, of which the mRNA-based vaccines by Moderna (Moderna, Cambridge, MA, USA) and BioNTech (BioTech, Mainz, Germany)/Pfizer (Pfizer, New York, NY, USA) have been identified as the most effective ones. The mRNA platform allowed rapid development of vaccines, but their global use is limited by ultracold storage requirements. Most resource-poor countries do not have cold chain storage to execute mass vaccination. Therefore, determining strategies to increase stability of mRNA-based vaccines in relatively higher temperatures can be a game changer to address the current global pandemic and upcoming new waves. In this review, we summarized the current research strategies to enhance stability of the RNA vaccine delivery system.

mRNA, a Revolution in Biomedicine

“…Viral vectors are genetically modified viruses containing genes of a virus partial completely replaced by antigen-encoding RNA [42,43]. Different viruses, such as pico viruses [44] and lentivirus [45] have been chosen for mRNA delivery, given their transfection capacity.…”

“…Due to their biocompatible and diversified properties, in addition to simple formulation with mRNA, with adequate and controlled release kinetics [26], viral vectors seem to be the most promising systems. Non-viral systems are mainly m Viral vectors are genetically modified viruses containing genes of a virus partially or completely replaced by antigen-encoding RNA [42,43]. Different viruses, such as picornaviruses [44] and lentivirus [45] have been chosen for mRNA delivery, given their high transfection capacity.…”

“…One of the main advantages of polymeric systems is the possibility of their modification to adapt them to the active substance. Biodegradable and mainly cationic polymers are commonly used to develop nanoparticle formulations with nucleic acids, leading to the formation of polyplexes [42,43]. The gold standard of polymeric vehicle, Polyethylenimine (PEI) has been proposed for mRNA delivery but its use has been limited due to its toxicity [50].…”

Thermostable Vaccines in Veterinary Medicine: State of the Art and Opportunities to Be Seized

“…The lack of thermostability has been proven to be one of the major barriers limiting the worldwide distribution of these products [4]. Indeed, the race to develop efficacious SARS-CoV-2 vaccines has resulted in the first available commercial vaccine products to have storage and delivery requirements of temperatures between +2 • C and −70 • C, depending on the product [5][6][7][8].…”

“…SPF chicken embryos,2 Freeze-dried,3 Freeze-dried Vero cell-adapted,4 Chimpanzee adenovirus vector,5 Double recombinant Vaccina virus,6 Transgenic peanut,7 Bacillus thurigensis vector,8 Foam-dried,9 NDV vector,10 Generated by reverse genetics system,11 Vaccina virus vector,12 NDV vector,13 Thermostability test according to Wen et al[86].…”