Getting a safe and effective COVID-19 vaccine from concept to approval in under a year is a remarkable scientific achievement that many doubted possible. As of date, there are 51 COVID-19 vaccine candidates in human clinical trials, and 13 are currently in advanced phase 3 trials1 of which 3 have already reported positive results2-4 and 1 was granted a temporary authorization for emergency use in the UK5 and in the US7. The Medicines & Healthcare Products Regulatory Agency (MHRA) in the UK was the first to grant the first Emergency Use Authorization (EUA) following a worldwide phase 3 trial to the COVID-19 vaccine from Pfizer/BioNTech, followed by the US Food and Drugs Administration (FDA) one week later. Other vaccine candidates, from Moderna/NIAID and AstraZeneca/University of Oxford, have also been submitted for US and European emergency regulatory approval and further regulatory decisions across the globe are expected in the coming days and weeks.
The Pfizer/BioNTech vaccine was the first vaccine to show positive early results from phase 3 trials and is the fastest vaccine to go from concept to reality. It is a new type of vaccine that contains the genetic instructions in the form of messenger RNA (mRNA) to produce the spike protein of SARS-CoV-2. The mRNA is encapsulated in lipid nanoparticles that help deliver the mRNA into the cells and prevent it from being degraded. The primary efficacy analysis of the phase 3 trial, based on 170 cases of COVID-19, demonstrated a vaccine efficacy rate of 95%2. Efficacy was consistent across age (including elderly people who are most vulnerable to COVID-19), gender, race, and ethnicity demographics included in the trials. Overall, the vaccine was well tolerated with no serious safety concerns reported during clinical trials although concerns about the risk of allergic reactions have arisen after the UK has started a mass vaccination campaign under EUA. The vaccine is given as two injections, 21 days apart. Immunity begins to kick in after the first dose, though a full protective effect is reached only seven days after the second dose. The limitation of this vaccine is that it must be kept at £ 70°C during shipment and storage to maintain optimal efficacy, making its distribution more difficult.
The Moderna/National Institute of Allergy and Infectious Diseases (NIAID) vaccine is also an mRNA vaccine containing the genetic instructions to produce the SARS-CoV-2 spike protein. The vaccine is injected twice 4-weeks apart and it has shown an efficacy rate of 94.1%, based on 196 cases of COVID-193. Once again, efficacy was consistent across age, race and ethnicity, and gender demographics. A significant advantage with the Moderna/NIAID vaccine is its improved storage stability. The vaccine lasts for up to 30 days in household refrigerators, up to 12 hours at room temperature, and is stable up to six months at £ 20°C. Thus, compared to the Pfizer/BioNTech vaccine, Moderna/NIAID vaccine has the advantage that it can be distributed using widely available vaccine delivery and storage infrastructures.
AstraZeneca/University of Oxford vaccine
The AstraZeneca/University of Oxford vaccine is based on a common cold virus called adenovirus that is engineered to express the SARS-CoV-2 spike protein. This vaccine was the first one to have detailed data from phase 3 trial published in a peer-reviewed journal6 thereby having its data widely and transparently available to the public. The study found that the vaccine was 62% effective at preventing COVID-19 when administrated as two similar doses one month apart. Interestingly, when volunteers were given a half dose followed by a full dose a month later, vaccine efficacy rose to 90%. However, this group did not include anyone over the age of 55, raising concerns that the higher efficacy may reflect the exclusion of an age group that is particularly vulnerable to COVID-19. Additional data will be required to clarify whether an initial lower dose could indeed confer better protection. Safety and efficacy data have now been submitted to regulators around the world. Compared to the vaccines from Pfizer/BioNTech and Moderna/NIAID, the technology used in the AstraZeneca/University of Oxford vaccine carries key advantages including the fact that the vaccine can be stored between 2°C to 8°C and can be produced, transported, and stored cheaply. Therefore, it can be effectively transported to undeveloped or developing countries. It is unclear what dosing AstraZeneca/University of Oxford are recommending their application requests for approval.
About the author:
Lúcia Moreira Teixeira is an expert in Immunology driven by a personal passion for science and the ambition to translate ground-breaking science into innovative life-changing immunotherapies. She is interested in immuno-oncology, autoimmune and infectious diseases. She strongly believes researchers should engage more in science communication. Find her on twitter – @LMTimmunol – or LinkedIn – www.linkedin.com/in/moreirateixeiralucia.
- WHO. Draft Landscape of COVID-19 Candidate Vaccines. (Publication of December 2, 2020). https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
- Pfizer November 18, 2020. Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints. https://www.businesswire.com/news/home/20201118005595/en/
- Moderna November 30, 2020. Moderna Announces Primary Efficacy Analysis in Phase 3 COVE Study for Its COVID-19 Vaccine Candidate and Filing Today with U.S. FDA for Emergency Use Authorization.
- AstraZeneca November 23, 2020. AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19. https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html
- Pfizer December 2, 2020. Pfizer and BioNTech Achieve First Authorization in the World for a Vaccine to Combat COVID-19.
- Voysey, M. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet (2020). https://doi.org/10.1016/S0140-6736(20)32661-1
- FDA December 11, 2020. FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine.