Abstract

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

Highlights

  • The outbreak of the COVID-19 pandemic [1,2,3,4], which was caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has triggered a global race to develop effective vaccines

  • Vaccination with whole spike protein has been shown to promote liver damage in treated animals [15] and, the use of only a part of this protein, such as the receptor-binding domain (RBD), which interacts with the angiotensin-converting enzyme 2 (ACE2) receptor protein, is considered to be the best alternative with respect to producing a safer vaccine [16]

  • Wolff et al demonstrated that intramuscular injection of nucleic acids resulted in the in vivo expression of a protein encoded by plasmid DNA [12], and it was later shown that vaccination with plasmid DNA can induce a strong immune response, as mentioned previously [22,23,24]

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Summary

Introduction

The strategy that has been employed for vaccine production needs to take into consideration the effect of the vaccine on the immune system and its efficacy against the virus, and the procedures for mass production, distribution, storage, and mass vaccination [5] To this end, the participating research groups are employing a diverse range of different formulations, techniques, and strategies to produce effective vaccines against SARS-CoV-2. The participating research groups are employing a diverse range of different formulations, techniques, and strategies to produce effective vaccines against SARS-CoV-2 In this regard, there are four main methods of vaccine development, namely, employing pathogens (inactivated or with low virulence) for the production of vaccines; recombinant protein vaccines; vector-based vaccines that include DNA vectors or viral vectors; and, the latest technology using RNA molecules for vaccination. We describe the use different adjuvants, which can be employed in order to enhance immunogenicity and establish an enduring immune memory

Traditional Vaccines
Next-Generation Vaccines
Recombinant Protein Vaccines
Plasmid DNA Vaccines
Viral Vector Vaccines
Retrovirus- and Lentivirus-Based Vectors
Adenovirus-Based Vectors
Adeno-Associated
RNA-Based
NP Formulation for RNA Delivery
Vaccine Adjuvants
Conclusions
Findings
Methods

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