COVID-19 mRNA Vaccines
The novel coronavirus disease 2019 (COVID-19), a pandemic induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses extreme health threats as well as tremendous economic loss worldwide. To contain the pandemic, herd immunity on a global scale is the major public priority. Therefore, in addition to developing corresponding therapeutics and diagnostics, scientists have rushed to develop COVID-19 vaccines since the discovery and publication of the virus’s genome. Based on the most promising vaccine technology platforms, there are currently at least 80 vaccines in clinical trials, and more than 70 in clinical development, involving viral vector–based vaccines, protein-based vaccines, and mRNA-based vaccines. Among them, the mRNA vaccine is based on a universal R&D and production platform, which is fast, large-scale, flexible, and cost-effective, and has the potential to respond to the pandemic threat. Here we give a brief summary of recently published data on COVID-19 mRNA vaccine candidates.
COVID-19
On March 11th, 2020, the World Health Organization (WHO) declared SARS-CoV-2 a global pandemic and named it the coronavirus disease 2019 (COVID-19). SARS-CoV-2 are spherical viruses with protrusions on their surfaces. Like SARS and MERS, the other human coronaviruses, SARS-CoV-2 consists of positive-sense, single-stranded RNA. The virus genome encodes a non-structural polyprotein and structural proteins, including spike protein (S), envelope protein (E), membrane protein (M) as well as nucleoprotein (N). Among them, S, E, and M proteins belong to the surface proteins, together create the viral envelope. While N protein holds the RNA genome and is abundant in coronavirus. In particular, S protein is a very important surface protein of coronavirus, which is closely related to the transmission ability of the virus. N protein is a highly immunogenic protein, involving genome replication and cell signaling pathway regulation, and is often used in the diagnosis of coronavirus.
Structure of the SARS-CoV-2 virus. (M) Membrane protein. (N) Nucleocapsid (capsid protein & RNA). (S) Spike protein. (L) Lipid bilayer. (Anand, P., et al, 2021).
COVID-19 mRNA vaccines
Compared with traditional vaccines, such as inactivated viruses, live attenuated and protein subunit vaccines, mRNA vaccines have overwhelming advantages, including rapid development and their versatility. In the preclinical and clinical trials, mRNA vaccines have been shown to have good safety and strong immunogenicity against viruses and cancers. Therefore, multiple researchers and companies are putting a lot of effort into developing mRNA vaccines against COVID-19. However, due to its nature of instability, technical limitations and other factors, mRNA vaccines were less attractive before the 21st century. Over the past decade, mRNA-based technology has evolved in synthesis, production, modification as well as delivery, which has promoted mRNA-based technology as a promising vaccine platform. And the pandemic of COVID-19 greatly gives opportunities to mRNA vaccine development.
Excitingly, there are two COVID-19 mRNA vaccines (including mRNA-1273 and BNT162b2) approved for the market and five other vaccine candidates are in various stages of clinical trials. Here, we list the currently available COVID-19 mRNA vaccines candidates in clinical trials.
Table 1 COVID-19 mRNA vaccine candidates in clinical trials.
| Name | Developers | Location | Route | Targets | Immunogenicity and protection | Safety | Phase |
|---|---|---|---|---|---|---|---|
| mRNA-1273 | Moderna | USA | IM | S-2P | Two doses of mRNA-1273 afforded an efficacy of 94.1% (95% credible interval, 89.3–96.8%) in preventing COVID-19. | Systemic adverse events were more common after the second vaccination. Serious adverse events were rare. | Phase IIIa NCT04470427 |
| BNT162b2 | BioNTech | Germany | IM | S-2P | The BNT162b2 vaccine with two injections showed 95% efficacy (95% credible interval, 90.3–97.6%) at preventing COVID-19. | The adverse events included mild-to-moderate pain at the injection site, fatigue, and headache. The frequency of serious adverse events was low and was similar in the vaccine and placebo groups. | Phase IIIa NCT04368728 |
| CVnCoV | CureVac AG | Germany | IM | S-2P | Neutralizing antibody titers in participants after two injections were comparable to those of convalescent human sera. | There were dose-dependent increases in frequency and severity of systemic adverse events, but the majority were mild or moderate and transient in duration | Phase III NCT04674189 |
| ARCoV | Abogen | China | IM | RBD | Two doses of ARCoV immunization elicited robust neutralizing antibodies and cellular immune responses in non-human primates and protected mice from SARS-CoV-2 challenge. | Not available. | Phase II ChiCTR2000039212 |
| ARCT-021 | Arcturus | USA | IM | Not available | Neutralizing antibody levels in both single-dose and prime-boost groups were within those observed in convalescent patient sera. | ARCT-021 was well tolerated, the majority of adverse local and systemic adverse events were mild. | Phase II NCT04668339 |
| LNP-nCoVsaRNA | Imperial College London | England | IM | S-2P | Two injections of LNP-nCoVsaRNA elicited higher neutralizing antibody titers than those of COVID-19 convalescent patients and cellular immune responses in mice. | Not available. | Phase I SRCTN17072692 |
| ChulaCoV19 mRNA vaccine | Chulalongkorn University | Thailand | IM | Not available | Not available. | Not available. | Phase I NCT04566276 |
a Represents that the vaccines have been approved for emergency use. (Huang, Q., et al, 2021)
With major advantages that rapid and scalable mRNA platform has the potential to encode any antigen, modified mRNA formulated with lipid nanoparticle (LNP) has emerged as an attractive platform for vaccines and therapeutics. Creative Biogene is a forward-looking research institute as well as a leading custom service provider in the field of mRNA-based drug research and development (R&D). Based on years of expertise in developing and optimizing mRNA molecules for medical purposes, we are now proud to offer a series of customized services to develop mRNA vaccines against infectious diseases. Our customers can contact our scientists directly for questions and learn about their project's progress at any time. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.
References
- Huang, Q., et al. (2021). “COVID-19 mRNA vaccines.” Journal of Genetics and Genomics.
- Anand, P., & Stahel, V. P. (2021). “Review the safety of Covid-19 mRNA vaccines: a review.” Patient Safety in Surgery, 15(1), 1-9.
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