mRNA COVID-19 Vaccines Receive Emergency Use Authorization in Historic Global First

By Du Xing

On December 2, according to a report by People's Daily Overseas Edition, a spokesperson for the UK Department of Health and Social Care stated that the government had accepted the recommendation of the Medicines and Healthcare products Regulatory Agency (MHRA) to approve the emergency use of the COVID-19 vaccine developed by Pfizer and the German biotechnology company BioNTech. The vaccine will be available across the United Kingdom starting next week.

The UK became the first country in the world to approve the emergency use of mRNA vaccines.

mRNA Vaccine

mRNA vaccines belong to the category of nucleic acid vaccines. Nucleic acid vaccines refer to plasmid vectors containing encoded protein gene sequences that are delivered into the host body through certain methods, where they express antigen proteins via host cells, thereby inducing an immune response against these proteins in the organism and achieving the goal of disease prevention. As a novel technology-based vaccine, nucleic acid vaccines are referred to as the third generation of vaccines, following whole-virus vaccines and recombinant subunit vaccines.

SARS-CoV-2 is a (+) single-stranded RNA virus. Its single-stranded RNA functions like mRNA in cells, allowing direct translation of encoded proteins within the cell, such as capsid proteins and viral RNA polymerase. COVID-19 vaccines developed using nucleic acid vaccine platforms can translate antigenic proteins in the human body, thereby inducing an immune response.

The advantage of mRNA vaccines lies in their simple and rapid production process. Unlike inactivated vaccines, mRNA vaccines require only the replication of viral nucleic acid to complete production, which greatly simplifies the manufacturing workflow and thus enables rapid vaccine production. However, the large-scale application of nucleic acid vaccines still faces many urgent technical challenges. First, nucleic acid vaccines exhibit low antigenicity, which is related to their expression levels in host cells; second, nucleic acids themselves have poor stability and require stringent temperature conditions for storage, typically needing ultra-low temperatures of -70°C; third, they are susceptible to degradation by nucleases in the body, necessitating suitable delivery vectors to transport them into the body.

BioNTech

Currently, BioNTech, Moderna, and CureVac are recognized as the three global leaders in mRNA therapeutics, with BioNTech and Moderna both at the forefront of COVID-19 vaccine development.

BioNTech, founded in 2008 and headquartered in Germany, offers a pipeline of cutting-edge products including personalized mRNA-based candidates, innovative chimeric antigen receptor T-cell (CAR-T) therapies, novel checkpoint immunomodulators, targeted cancer antibodies, and small molecules.

On November 18, Pfizer and BioNTech announced that the final results of their Phase III clinical trial showed a total of 170 confirmed cases among 43,000 participants, with 162 cases in the placebo group and only 8 in the vaccine group, indicating that BioNTech’s mRNA vaccine has an efficacy rate as high as 95%. Following this announcement, Pfizer’s stock rose by 3%, while BioNTech’s surged by 10%.

Moderna, Inc.

Moderna, founded in 2010 and headquartered in Cambridge, Massachusetts, USA, focuses on messenger RNA (mRNA) research and is committed to becoming a pioneer and leader in global mRNA drug discovery and development. Currently, the company’s pipeline comprises 21 vaccine and drug candidates: its SARS-CoV-2 (COVID-19) vaccine is in Phase III clinical trials; four candidates, including the cytomegalovirus (CMV) vaccine and personalized cancer vaccines, are in Phase II clinical trials; and eight candidates are in Phase I clinical trials. Notably, 18 of the 21 candidates in Moderna’s pipeline are mRNA-based therapeutics and vaccines.

On November 30, Moderna released the final data from its vaccine trial. Among 30,000 participants, 196 contracted COVID-19, including 30 cases of severe disease. Of the 196 confirmed cases, 185 were in the placebo group and only 11 were in the vaccinated group, indicating that the vaccine’s efficacy in preventing SARS-CoV-2 infection was 94.1%, with 100% efficacy against severe cases. Although the final efficacy rate was slightly lower than the 94.5% reported in the interim Phase III analysis, it far exceeded the FDA’s minimum requirement of 50% efficacy for vaccine approval.

Comparison of Two Vaccines

Although both are mRNA vaccines, there are differences between BioNTech’s mRNA vaccine and Moderna’s mRNA vaccine.

From the perspective of efficacy, the two are evenly matched. BioNTech’s mRNA vaccine has an efficacy rate of 95%, while Moderna’s mRNA vaccine has an efficacy rate of 94.1%, making them equally effective.

From the perspective of adverse reactions, the two parties are evenly matched. Both sides claim that there are no serious adverse reactions, but considering that mRNA vaccines are a brand-new technology, further observation in Phase IV clinical trials is still required in the future.

From the perspective of storage temperature, the Moderna vaccine prevails. The vaccines developed by BioNTech and Pfizer have extremely stringent storage requirements, necessitating preservation at -70°C. In contrast, Moderna’s mRNA vaccine can be stored for six months at -20°C, for one month in standard refrigerators at 2–8°C, and even for 12 hours at room temperature, significantly enhancing its accessibility. Given that each ultra-low temperature freezer typically costs between $5,000 and $15,000, this poses a challenge for healthcare institutions in developing countries.

From a pricing perspective, the BioNTech vaccine is more competitive. Currently priced at $19.5 per dose, it is cheaper than Moderna’s vaccine, which costs between $25 and $37 per dose.

In terms of production capacity, the BioNTech vaccine prevails. BioNTech plans to supply 1.3 billion doses globally in 2021, while Moderna expects its 2021 production capacity to reach 500–1 billion doses.