Perspectives on RNA Vaccine Candidates for COVID-19

Abstract

With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.

SARS-CoV-2 spike protein: pathogenesis, vaccines, and potential therapies

“…Similar to Pfizer-BioNTech and Moderna, the vaccine encodes the SARS-CoV-2 S protein gene that is encapsulated by a lipid-soluble nanoparticle [ 19 ]. However, CureVac’s vaccine keeps the natural non-chemically modified mRNA nucleotides sequence rather than substituting Uridine with pseudouridine in the other vaccines [ 13 , 19 ], Dolgin). This vaccine has been expected to owe some advantages over its mRNA vaccine competitors since it can be stored at standard refrigerator temperature, and requires a lower dosage of 12 μg, thus, providing a faster and cheaper mass production.…”

A Minireview of the Promising Drugs and Vaccines in Pipeline for the Treatment of COVID-19 and Current Update on Clinical Trials

“…There has been an increased focus on the pre-clinical development of COVID-19 vaccines by many research institutes and vaccine manufacturers around the world. Currently, the predominant vaccine platforms for pre-clinical studies included are DNA, RNA, inactivated virus, viral vector (Replicating and Non-Replicating), live attenuated virus, protein subunit and virus-like particle (VLP) ( Bezbaruah et al, 2021 ; Borah et al, 2021 ). Though many vaccines have been included in clinical trials, vaccine candidates such as AZD1222 (Covishield, Vaxzevria), BNT162b2 mRNA-1273 and CoronaVac are in the phase IV clinical trial ( Table 2 ).…”

Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2

“…(i) compared to DNA vaccines, mRNA vaccines have no confirmed mechanism by which they would permanently modify the DNA of the affected cells. They are thus less prone to host genome integration and anti-vector immunity (a compromising factor of viral vectors) [42], with no potential for integration into host genome [43];…”

“…Diverse vaccine technology platforms have been developed for COVID-19, including nucleic acid (RNA and DNA), protein subunit, virus-like particles, inactivated virus, viral vectors and live attenuated virus [14,15]. The recent interest in mRNA vaccines has been boosted by technological developments that have enhanced mRNA stability and improved vaccine delivery (Borah et al, 2021). Ultimately, the development of mRNA vaccines did not start from scratch but was built on more than 30 years of experience of the scientific community aimed to develop injectable mRNA compounds [16].…”