top of page
Search
Nov 24, 20209 min read

A Snapshot of the covid-19 vaccines: Pfizer, Moderna and Astra Zeneca

Updated: Dec 6, 2020



During these past few days, we have seen numerous headlines regarding the promising results of covid-19 vaccine trials from Pfizer and Moderna. As of this writing, Astra Zeneca also published their press release yesterday also with some good news.


While the vaccines are still waiting for approval from the regulators, we can only imagine how close the light at the end of the 2020 tunnel is. This blog will explore the concept of vaccines and the vaccine technology involved regarding the three covid-19 vaccines (Pfizer, Moderna, and Astra Zeneca). Furthermore, it will also include some information from current press release updates.


What are vaccines?

Vaccines are substances that stimulate an immune response. The aim of vaccination is to train the body to fight against specific pathogens before it causes a disease. Several infectious diseases of today are reduced or have been prevented because of vaccination. Immunisation and vaccination are terms that often are used interchangeably but vaccination is the “the act of introducing a vaccine to the body to produce immunity to a specific disease” while immunization refers to the “process by which a person becomes protected against a disease through vaccination (CDC, 2018).


How do vaccines work? Image by Creazilla / CC0 1.0


Vaccine Classifications

There are different classifications of vaccines. This blog will only concentrate on the types that Pfizer, Moderna, and Astra Zeneca / Oxford University developed for covid-19.


· Viral-vector based vaccine – This type utilises a weakened virus (either done chemically) as transport for a part of a pathogen to initiate an immune response.


The ChAdOx1 nCoV-19 vaccine is a viral vector based vaccine. The glycoprotein spike region of the coronavirus is encoded into a weakened type of a common cold adenovirus. The adenovirus is engineered genetically so that this becomes incapable for human viral spread (Folegatti et al., 2020).


Viral-vector based vaccine technology is not new and scientists involved already have years of experience in this area of gene therapy. A "general" disadvantage for viral vector vaccines is that this cannot be given to individuals who are immunocompromised due to the risk of developing an infection from the weakened viral transport (Funk, Laferriere & ardakani, 2020).


Covid-19 Oxford Vaccine Trial. Image from

Oxford Vaccine Group at the University of Oxford (2020)



· mRNA based vaccine – uses mRNA to provide instructions for cells to produce a protein (or antigen) specific to the pathogen. Messenger ribonucleic acid or mRNA for short, is “a single-stranded RNA molecule that is complementary to one of the DNA strands of a gene” (National Human Genome Research Institute, n.d.). Messenger RNA’s carry the protein blueprint to ribosomes which are parts of the cell that acts like a machine to produce specific proteins (Clancy, 2008). With these mRNA vaccines, the mRNA is being read by the ribosomes of cells so that proteins can then be synthesized.


Pfizer and Moderna vaccines for covid-19 are both mRNA based in which the aim is to introduce mRNA to the cell so that the cell can be instructed to produce immunogenic proteins which will then cause the formation of antibodies and T-cell response. This enables the immune system to recognise & fight the virus should it try to infect. However, the primary clinical endpoints for the studies of these vaccines were focused on the experienced clinical symptoms of covid-19. It would be great to also know if these vaccines also prevent the infectivity of the virus (Seheult, 2020).


A summary of how mRNA vaccines work


Moderna is a pioneer in mRNA therapeutics. It should also be noted that there has been no approved RNA based vaccine to date but some clinical testings have been made using this technology for other viruses such as rabies and influenza (Funk, Laferriere & Ardakani, 2020).


If the Pfizer and Moderna vaccines for covid-19 gets the heads up from the regulators for use for the public, they will then be the first two approved mRNA vaccines in history.


An example of the process involved

in the creation of mRNA vaccines.

Image taken from Yi, C., Yi, Y. & Li, J. (2020)

A short video about the Moderna vaccine (mrNA-1273)


· Other vaccine classifications: Of course there are other types of vaccine classifications which will not be focused further in this blog. These classifications include live attenuated vaccines, inactivated vaccines, conjugated vaccines, toxoids and subunit vaccines. If you are interested to know more about these types, please see link below:




How are data analysed for vaccine trials?

In general, newly developed vaccines are studied in phases and will be tested to thousands of volunteers at phase 3. Studies can be blinded, meaning the volunteer nor the one who administers the vaccine do not know if the injected substance is the vaccine of study or placebo (or possibly another vaccine which is already approved depending on study arm design). This is done for comparison as well as to avoid possible bias.


The volunteers will then be followed-up and evaluated based on endpoints (which can be primary or secondary). Endpoints are the study objectives or aims. The volunteers will be observed if they got infected with covid-19 post administration. Should they get covid or develop symptoms, they will then be evaluated further to see if the ones infected are in the vaccine group or the placebo (or another vaccine for comparison). The effectivity of the vaccine will then be based on the statistical analyses in relation to the endpoints. This is just a general picture of how the trials are analysed but in practice, it can be more than as described as studies usually have multiple primary and secondary endpoints.


Let's take a closer look at the vaccines


The Pfizer Vaccine for covid-19


Vaccine name (in clinical trials): BNT162b1 (phase 1); BNT162b (phase 2); BNT162b3 (administered using a prime/boost regimen)


Vaccine technology: mRNA based


Current updates:

· A peer-reviewed published data is yet to be expected but Pfizer-BioNTech made official statements in their press release on the 18th of November 2020 indicating that their vaccine has a 95% effective rate. From the press release, it is mentioned that the vaccine was found to be 95% effective against COVID-19 beginning 28 days after administration of the first dose. This is based from the findings of the primary efficacy analysis. They evaluated 170 COVID-19 confirmed cases and upon unblinding (since the study is a blinded study), 162 were in the placebo group, and 8 were in the vaccine group. Also further mentioned in the press release is that the vaccine was well tolerated among the 43,000 enrolled participants with no serious concerns on safety observed (Pfizer, 2020).


· What is also known about the vaccine is that it needs to be stored in very cold temperatures to maintain stability of the mRNA. When kept at 25 F (-3.89 C), the vaccine can be stored for 5 days. When kept at -94F (-70 C), the vaccine can be stored for 6 months (Seheult, 2020). Therefore, there will be challenges in distributing it at a wordwide scale because of the need to be kept at containers that maintain the specific temperature for the vaccines to be still effective upon administration.


 

The Moderna vaccine for COVID-19


Vaccine name (in clinical trials): mRNA-1273


Vaccine technology: mRNA based


Current updates:

· Moderna published their press release on recent updates on the 16th of November 2020. Their study enrolled more than 30,000 participants. Phase 3 of the study (COVE study) revealed an efficacy rate of 94.5% (p<0.0001) as per first interim analysis. This included the 95 confirmed covid-19 participants. Of the 95 cases, 90 were in the placebo group while there were 5 observed in the vaccine group. Out of these 90 participants in the placebo arm, 11 were observed to have severe cases of covid-19 and zero (0) cases were recorded for the vaccine arm (n=5) (Moderna, 2020)


· When the vaccine is kept at 25 F (-3.89 C), it can be stored and will be good for 1 month (Seheult, 2020). Challenges on storage is the same as the Pfizer vaccine which involves storing it at containers that maintain cold temperatures to still keep the mRNA intact.


 

The Astra Zeneca / Oxford University vaccine


Vaccine name (in clinical trials): AZD1222 (formerly ChAdOx1 nCoV-19)


Vaccine technology: Viral Vector-Based (Nonreplicating)


Current updates:

· Researchers at the University of Oxford just published their safety and immunogenicity data for the ChAdOx1 nCoV-19 vaccine (in phase 2/3) administered in a prime-boost regimen in young and old adults. According to the published document from The Lancet, the vaccine "appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose" and that "further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities."


· On the 23rd of November 2020, AstraZeneca announced in their press release that the vaccine resulted to an average efficacy rate of 70% based on the analysis of combined dosings. A vaccine efficacy rate of 90% was observed in one dosing regimen (n=2,741) which involves the administration of a half dose, and then followed by one full vaccine dose after a month.


In another dosing regimen (n=8,895), the vaccine showed an efficacy rate of 62% which involves the administration of two full doses with each dose given at least a month apart.


The overall efficacy rate of 70% is a result of the combined analysis of the two dosing regimens (Astra Zeneca, 2020). So in practice, it is possible that once approved, the dosing will be standardised to the regimen which involves giving the half dose first followed by a full dose booster shot a month after as this resulted to a higher efficacy rate. But this will depend on the review from the regulators as well as the final decisions made by the involved key clinical decision makers.


· The vaccine is stable at 2-8 C fridge temperature (BioTechScope, 2020)


 

What’s next for these vaccine trials?

As of this writing, the three vaccines are waiting for regulatory approvals so that they can be given to millions of people worldwide. Since giving it will be done on a massive scale, the production, logistics and the delivery of these vaccines will be very challenging especially in reaching the far corners of the world. It is widely discussed that these vaccines will be given in phases with frontline workers such as health care providers being the first to receive the doses and then next to be provided to those who are in the vulnerable groups, and then hopefully to the wider population.


Eradicating diseases is not a new thing as far as history is concerned. Since the time of Edward Jenner in the world's fight against smallpox and also during the time of the discovery of penicillin by Edward Fleming (who is also from Oxford University) which enabled the world to fight against so many bacterial related infections not to mention that penicillin is still being used today, we can’t help but be optimistic of the future and be thankful of Science as well as appreciate the efforts made by the people involved in the fight against covid-19. Thanks to the doctors, nurses and the rest of the frontline workers. Non-frontlline individuals also contributed huge in flattening the curves of their respective geographical locations by staying at home, performing hand hygiene measures and maintaining physical distancing. Each and everyone has his/her contribution in the fight. It is a worldwide effort. We hope that in a few weeks time, some progress will be made on the approvals of these covid-19 vaccines and treatments. In a few months or years to come, hopefully the world can then go back to its "old normal".

 

Disclaimer:

The content in this blog is for informational purposes only and should not be taken as medical advice. It is always best to consult your doctor for medical questions that you might have.


If you are a healthcare provider, the content here should not be used to make any diagnosis, give advice or prescribe treatment as this blog is for informational and educational purposes only. Healthcare is an everchanging field and each patient is unique. It is your responsibility as a healthcare provider to always refer to current care standards and practices.


 

References:


BioTechScope. 2020. Oxford University’S Fridge Stored COVID-19 Vaccine Is 90% Effective. [online] Available at: <https://biotechscope.com/oxford-universitys-fridge-stored-covid-19-vaccine-is-90-effective/> [Accessed 23 November 2020].


British Society for Immunology, (n.d.). How Vaccines Work. [online] Immunology.org. Available at: <https://www.immunology.org/celebrate-vaccines/public-engagement/guide-childhood-vaccinations/how-vaccines-work> [Accessed 22 November 2020].


Centers for Disease Control and Prevention, 2018. Immunization Basics. [online] Cdc.gov. Available at: <https://www.cdc.gov/vaccines/vac-gen/imz-basics.htm> [Accessed 22 November 2020].

Clancy, S., 2008. RNA Functions. [online] Nature.com. Available at: <https://www.nature.com/scitable/topicpage/rna-functions-352/> [Accessed 23 November 2020].


Folegatti, P.M., Ewer, K.J., Aley, P.K., Angus, B., Becker, S., Belij-Rammerstorfer, S., Bellamy, D., et al. (2020), “Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial”, The Lancet, Elsevier BV, Vol. 396 No. 10249, pp. 467–478.


Funk, C.D., Laferrière, C. and Ardakani, A. (2020), “A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic”, Frontiers in Pharmacology, Frontiers Media SA, Vol. 11, available at:https://doi.org/10.3389/fphar.2020.00937.


Moderna (2020). Moderna’S COVID-19 Vaccine Candidate Meets Its Primary Efficacy Endpoint In The First Interim Analysis Of The Phase 3 COVE Study. [online] Moderna, Inc. Available at: <https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy> [Accessed 24 November 2020].


Oxford Vaccine Group at the University of Oxford (2020). Covid-19 Oxford Vaccine Trial. [image] Available at: <https://covid19vaccinetrial.co.uk/about> [Accessed 23 November 2020].

Seheult, R. (2020). Coronavirus Update 117: Moderna Vs. Pfizer COVID 19 Vaccine (Mrna Vaccines). [video] Youtube uploaded by Medcram. Available at: <https://www.youtube.com/watch?v=eZvsqBCvB00> [Accessed 23 November 2020].


Pardi, N., Hogan, M., Porter, F. et al. (2018). mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov17, 261–279 DOI: https://doi.org/10.1038/nrd.2017.243


Pfizer (2020). Pfizer And Biontech Conclude Phase 3 Study Of COVID-19 Vaccine Candidate, Meeting All Primary Efficacy Endpoints. [online] Pfizer.com. Available at: <https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine> [Accessed 23 November 2020].


University of Oxford (2020). Oxford COVID-19 Vaccine Begins Human Trial Stage. [online] Ox.ac.uk. Available at: <https://www.ox.ac.uk/news/2020-04-23-oxford-covid-19-vaccine-begins-human-trial-stage> [Accessed 22 November 2020].


Vaxcyte (2020). Conjugate Vaccines. [online] Vaxcyte. Available at: <https://vaxcyte.com/conjugate-vaccines/> [Accessed 22 November 2020].


Yi, C., Yi, Y. & Li, J. (2020). mRNA Vaccines: Possible Tools to Combat SARS-CoV-2. Virol. Sin. 35, 259–262. https://doi.org/10.1007/s12250-020-00243-0

124 views0 comments

Recent Posts

See All

Comments

bottom of page