COVID-19 vaccines

COVID-19 vaccines

COVID-19 is a disease caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus was first detected in Wuhan, China, in December 2019 and has led to a Pandemic, announced by the World Health Organization on 11thMarch 2020.

This page provides the following information:

  • Key facts about COVID-19 vaccines
  • Pfizer BioNTech vaccine
  • Oxford AstraZeneca vaccine
  • Who should have the vaccines?
  • Safety and side effects
  • Vaccine ingredients
  • Nucleic acid and viral vector vaccines explained

Key vaccine facts

COVID-19 (coronavirus disease) is an emerging disease caused by a newly discovered coronavirus. It can result in severe illness and death, particularly for people in risk groups. COVID-19 presents with a range of symptoms of varying severity. Asymptomatic infection also occurs, and it is predicted that between 20–30% of people who have the virus do not show symptoms. For around 80% of people who have symptomatic COVID-19, symptoms range from mild and without hypoxia (low level of oxygen in the blood) to moderate, including non-severe pneumonia.

Surveillance studies have shown that 15% of people with symptomatic COVID-19 have significant disease including severe pneumonia, and 5% experience critical disease with life-threatening complications. Critical disease includes acute respiratory distress syndrome (ARDS), sepsis, septic shock, cardiac disease, thromboembolic events, such as pulmonary embolism and multi-organ failure. Most of the fatalaties from COVID-19 complications have been in individuals of older age or with underlying health conditions.

There is growing evidence that in those who develop critical COVID-19 disease, there can be longer-term consequences such as rare neurological and psychiatric complications. These may include stroke, delirium, anxiety, depression, damage or inflammation of the brain, and sleep disturbances. Refer to the long-term health effects guidance for further information on commonly reported symptoms and services available for recovering COVID-19 patients.

Some risk factors are associated with a higher chance of developing severe or critical COVID-19 disease. These are:

More information about COVID-19 disease, including the global impact of the pandemic see: Coronavirus (COVID-19)

It is recognised that a vaccine is urgently needed to prevent people from becoming severely ill and dying from COVID-19. The aim of the UK COVID-19 vaccination programme is to protect those who are most at risk. In response to the COVID-19 pandemic, scientists around the world have come together to focus their efforts on developing vaccines to prevent people from becoming infected with the coronavirus. Over 270 vaccines are in various stages of development, and some of these utilise similar technologies to existing vaccines in use, whilst others involve newer approaches. 

Although clinical trials have been completed more rapidly during the pandemic, this has been achieved by overlapping the different stages (phase 1, 2 and 3) of clinical testing rather than completing them sequentially. Assessment of safety has not been compromised and the trials have been subject to the same strict regulatory requirements as any other vaccine studies. Each of the vaccines that has received or is under review for temporary licensing have been tested in trials with over 20,000 people, collecting many months of safety follow-up data. In many cases, these trials are larger than trials for other drugs and vaccines which have been licensed.

See below for information about how vaccines are developed and how some of the administrative processes were speeded up during the COVID-19 pandemic. With thanks to Nature for permission to use this video.

In the UK, two vaccines are currently in use, following regulatory approval. These are the BNT162b2 vaccine, developed by Pfizer and BioNTech and the ChAdOx1 nCoV-19 (AZD1222), developed by the University of Oxford and AstraZeneca. Both of these vaccines have been authorised for emergency use by the Medicines and Healthcare products Regulatory Agency (MHRA), as well as a vaccine developed by Moderna, which is expected to be available from Spring 2021. For more information about how vaccines are licensed, see How vaccines are tested, licensed and monitored.

 

 

Pfizer-BioNTech BNT162b2 vaccine

The BNT162b2 vaccine is a COVID-19 mRNA vaccine developed by Pfizer and BioNTech. It contains the genetic code (mRNA) of the spike protein, which is found on the surface of the SARS-CoV-2 virus. Once inside the body, the spike protein is produced, causing the immune system to recognise it and initiate an immune response. 

This means that if the body later encounters the spike protein of the coronavirus, the immune system will recognise it and destroy it before causing infection. As there is no whole or live virus involved, the vaccine cannot cause COVID-19 disease. The mRNA is naturally degraded after a few days. More information about mRNA vaccines is below.

The safety and efficacy of the BNT162b2 vaccine have been assessed in clinical trials of over 44,000 people in six countries: USA, Germany, Brazil, Argentina, South Africa and Turkey. The trial reported that the vaccine can prevent 95% of COVID-19 cases. This means that in a group of 20 people who are vaccinated, if all are exposed to the coronavirus, 19 people will be prevented from getting COVID-19. The trial also showed that the vaccine provides similar protection in people of all ages, races and ethnicities.

The BNT162b2 vaccine is a two-dose course, which is given as an injection into the upper arm. The second dose can be given 3-12 weeks after the first dose. 

Oxford-AstraZeneca ChAdOx1 nCoV-19 (AZD1222)

The ChAdOx1 nCoV-19 vaccine was developed by the University of Oxford and AstraZeneca. The vaccine works by delivering the genetic code of the SARS-CoV-2 spike protein to the body’s cells, similarly to the BNT162b2 vaccine. Once inside the body, the spike protein is produced, causing the immune system to recognise it and initiate an immune response. This means that if the body later encounters the spike protein of the coronavirus, the immune system will recognise it and destroy it before causing infection.

This Oxford-AstraZeneca vaccine uses the ChAdOx1 technology, which has been developed and optimised by the Jenner Institute over the last 10 years. This type of vaccine technology has been tested for many other diseases such as influenza (flu) and middle east respiratory syndrome (MERS), another type of coronavirus. More information about viral vectored vaccines is below.

The ChAdOx1 nCoV-19 vaccine has been tested by the University of Oxford in clinical trials of over 23,000 people in the UK, Brazil and South Africa. AstraZeneca are also running a further trial with 40,000 people in the USA, Argentina, Chile, Columbia and Peru. 

Interim results from the UK and Brazil trials showed that the vaccine can prevent 70.4% of COVID-19 cases. This was calculated across two different groups of people, who received two different dose regimens. The vaccine was shown to prevent 73% of cases in individuals with at least one underlying health condition. The vaccine has also been shown to produce similar immune responses in older adults when compared with young, healthy individuals, although the efficacy data for this group is not yet available.

The ChAdOx1 nCoV-19 vaccine is given as a two-dose course, which is given as an injection into the upper arm. The second dose is given 4-12 weeks after the first dose. 

Safety and side effects

The COVID-19 vaccines currently approved have been thoroughly reviewed by the Medicines and Healthcare products Regulatory Agency in the UK (the MHRA). The regulatory team have completed a full review of the safety information reported from the trials, which includes several months follow-up data from 23,000 people for the Oxford-AstraZeneca vaccine and 44,000 people for the Pfizer-BioNTech vaccine.

This means that the MHRA has reviewed all the information from the clinical trials of these vaccines, which includes assessing all the side effects and medical conditions that people in the trials experienced.  

The number of illnesses reported in the vaccinated group is compared with the control group, to see whether the vaccine could be associated with an increase in any medical conditions. The rates of illness are also compared with the rate of those illnesses in the general population. For any severe illnesses reported, a specialist doctor involved in treating the person and an independent safety committee consider whether the illness could be associated to the vaccine.

All the information about adverse events (unexpected illnesses) reported during the trial has been provided to the regulators, and the safety profile of both the Oxford-AstraZeneca and the Pfizer BioNTech vaccines is similar to that of other vaccines.

Expected side effects

Because vaccines work by triggering your immune system to produce a reaction, you can however have side effects after you receive the vaccine that feel similar to having a real infection.  Things like having a fever, or feeling achey, or getting a headache (often described as “flu-like” symptoms) are common after receiving many vaccines and this is the same for the approved COVID-19 vaccines.  Having these symptoms means that your immune system is working as it should be.  Usually, these symptoms last a much shorter time than a real infection would (most are gone within the first 1-2 days).

The common side effects associated with the currently approved vaccines are below. These symptoms generally last 1-2 days following vaccination. 

For more information on side effects, ask for the Patient Information Leaflet for the vaccine you are offered. Full information about side effects is available here:

Oxford-AstraZeneca ChAdOx1 nCoV-19

Pfizer-BioNTech BNT162b2

None of the currently approved vaccines are using a live SARS-CoV-2 virus in them; so you cannot get COVID-19 from them.  

Who should have the vaccines?

The aim of the COVID-19 vaccination programme is to protect those who are most at risk of becoming seriously ill with COVID-19.

Following advice from the UK Joint Committee on Vaccination and Immunisation, the programme will vaccinate people in the order of highest risk of severe COVID-19 disease, due to occupation, age or other risk factors. The categories are outlined below:

At-risk groups included in priority group 6 are:

  • Chronic respiratory disease (including severe asthma)
  • Chronic heart disease and vascular disease 
  • Chronic kidney disease
  • Chronic liver disease
  • Chronic neurological disease
  • Diabetes
  • Immunosuppression
  • Dysfunction of the spleen
  • Morbid obesity
  • Severe mental illness
  • Adult carers
  • Younger adults in long-stay care homes

Immunosuppression

People whose immune systems do not work normally, either because of a medical condition or treatment, are being recommended to have the COVID-19 vaccines at present. There is no concern that these vaccines will cause harm in people with immunosuppression, but there is a chance that they may not get as much protection from any vaccine received. This is because for a vaccine to work well, your immune system needs to make a strong response to it.  Any condition or treatment that reduces the function of the immune system can reduce the response to a vaccine.

 

Who can’t have the vaccines? (Contraindications)

Pregnancy and breastfeeding

None of the trials conducted on the currently available vaccines have included pregnant or breastfeeding women. There have, however, been people who became pregnant during the trials, and they and their babies are being monitored closely.  At the moment, there isn’t any sign that these vaccines cause harm to pregnant women or the unborn baby. However, there isn’t yet enough data to say that they should be given in pregnancy. It is expected that there will be more trials and data on this in future. 

For cases where a pregnant woman is at high risk of exposure to the virus or they are at very high risk of having serious complications from COVID-19, they should discuss the risks and benefits of being vaccinated with their clinician.

The JCVI recommended that women who are breastfeeding may be offered both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. There is no known risk associated with receiving non-live vaccines whilst breastfeeding.

Children

Children and young people have a very low risk of becoming seriously ill from COVID-19 disease compared to adults. At the moment, children under the age of 16 have not been included in the vaccination recommendations. Some children with complex medical conditions may be advised to receive a COVID-19 vaccine, but this assessment will be made on an individual basis. Clinical trials are being planned or already underway to provide evidence for use in this age group.

Allergies

There were no serious allergic reactions during any of the trials of these vaccines. None of these trials included participants who were known to have severe allergies. After the Pfizer-BioNTech vaccine was rolled out in the UK, two people had severe reactions (anaphylaxis) caused by an ingredient in the vaccine. Both individuals already had severe allergies and carried emergency adrenaline pens. 

The Pfizer-BioNTech and Oxford-AstraZeneca vaccines should not be given to those who have had a previous severe allergic reaction to:

  • A previous dose of the same COVID-19 vaccine
  • An ingredient in of the COVID-19 vaccine

The Pfizer-BioNTech vaccine contains polyethylene glycol (PEG) which is in a group of known allergens commonly found in medicines. The Oxford-AstraZeneca vaccine does not contain PEG, so those with allergies to this ingredient can receive the alternative vaccine. 

Additional information about anaphylaxis and adverse reactions to vaccines can be found here.

Vaccine ingredients

For full information on ingredients, ask for the Patient Information Leaflet for the vaccine you are offered. Common ingredients used in vaccines, and present in both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines are:

The active ingredient of the Pfizer-BioNTech vaccine is BNT162b2, which contains the genetic code for the coronavirus spike protein, inside a lipid (fat) capsule. The vaccine also contains other inactive ingredients such as cholesterol. 

The active ingredient of the Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine is made from a modified adenovirus which causes the common cold in chimpanzees. This virus has been modified so that it cannot cause an infection. It is used to deliver the genetic code for the coronavirus spike protein. The vaccine also contains inactive ingredients such as polysorbate 80, an emulsifier, and a very small amount of alcohol (0.002mg per dose). The vaccine also contains traces of magnesium (3 to 20 parts per million).

All vaccine ingredients are present in very small amounts and there is no evidence that they can cause harm in these amounts. The Pfizer-BioNTech and Oxford-AstraZeneca vaccines do not contain:

  • Human or animal products
  • Common allergens such as latex, milk, lactose, gluten, egg, maize/corn, or peanuts

Both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines use genetic technologies to generate an immune response. More information about these technologies is below.

 

The manufacturing process for the Oxford-AstraZeneca vaccine involves the production of a virus, the adenovirus, which carries the genetic material to the cells inside the body. To produce this virus in the laboratory, a “host” cell line is needed. For some vaccines, chicken cells are used for this process, and for other human cell lines are used to produce the virus. The Oxford-AstraZeneca vaccine uses a cell line called HEK-293 cells. 

HEK-293 is the name given to a specific line of cells used in various scientific applications. The original cells were taken from the kidney of a legally aborted foetus in 1973. HEK-293 cells used nowadays are clones of those original cells, but are not themselves the cells of the aborted foetus.

Other therapeutic products which use HEK-293 cells as a producer cell line include Ad5 based vaccines, such as Cansino’s COVID-19 vaccine, Adeno associated viruses (AAV) and lentiviruses as gene therapy vectors for various diseases. Many of these products are in clinical trials.

See also, information about the use of human cell lines in the production of vaccines

Nucleic acid and viral vectored vaccines explained

Newer vaccines such as mRNA vaccines and viral vectored vaccines, including the Oxford ChAdOx1 nCoV-19 vaccine differ from many traditional vaccines in the way they activate the immune system. Most traditional vaccines inject the antigen (part of the disease that stimulates an immune response) directly into the body. See types of vaccine for information about how different types of vaccines work. 

In contrast, these two newer approaches deliver the genetic instructions for the antigen to the body’s cells. The cells then manufacture the antigen which goes on to stimulate the immune response. Injecting genetic material has raised questions about the use of these vaccines, such as whether they can modify the DNA of those receiving them. Here, we will explain why this is not possible.

Firstly, we will look at how cells normally manufacture proteins. Our DNA (DeoxyRibonucleic Acid) is safely packaged inside the nucleus of a cell and cannot leave. Within this DNA are gene sequences, and each gene encodes the blueprints for making one of the proteins the body needs. To make a protein the first step is to transcribe DNA into mRNA (messenger Ribonucleic Acid) using a special enzyme (or “tool”) called RNA polymerase. This step is a one-way process as cells are unable to transcribe RNA back into DNA. 

Unlike DNA, mRNA is free to leave the nucleus as it has a pass that allows it to exit. However, this pass is one way and once it leaves, the mRNA cannot return. Once it has left the nucleus the mRNA links up with the special cellular machinery in the cytoplasm. This machinery uses the information coded in the mRNA to make new proteins. As with the process of going from DNA to mRNA this process is also one-way, and it’s not possible to go backwards from protein to mRNA. These proteins may be used inside the cell or transported out of the cell for use elsewhere in the body.

The COVID-19 mRNA vaccines take advantage of this internal process to make copies of the spike protein, which usually appears on the surface of the coronavirus. There are two types of vaccine which use this process:

mRNA vaccines

In this type of vaccine, mRNA is delivered to the cell inside a lipid membrane. Once the mRNA is inside the cell, the same machinery that is used to make our own proteins can make the spike protein. This mRNA has no way of getting into the nucleus where our DNA is. Even if it could, mRNA cannot fuse with DNA and as with our own mRNA, has no way of getting translated back to DNA. As such, there is no way for human DNA to be altered by an mRNA vaccine. This mRNA lasts a few days before the cell removes it, but in that time we have produced a lot of spike protein to stimulate the immune response.

Viral vectored vaccines

Viral vectored vaccines work in a different way. The genetic information inside a viral vectored vaccine like ChAdOx1 is DNA rather than RNA. This DNA is a short linear piece of double stranded DNA which contains the viral genes along with the gene for the spike protein. The viral vector first infects the cell and then delivers this DNA to the cell nucleus. The cell can then transcribes the viral genes (DNA) into mRNA using the same RNA polymerase it uses for our own genes. After transcription, the mRNA gets tagged so it can leave the nucleus and be made into spike protein by the cell machinery. 

In the Oxford vaccine, the viral gene that is required to replicate viral DNA has been removed. As viruses use a different process to human cells to replicate their DNA, the cell itself cannot replicate viral DNA either. This means the viral vector cannot replicate (make more viruses) or cause disease. Both the original viral DNA and the spike protein mRNA only last a few days before the cell removes them. Such design features alongside a cell’s natural DNA protection measures, prevents any possibility of viral DNA integrating with human DNA.

For more information about the new types of COVID-19 vaccines, see The Race for Coronavirus Vaccines.

Page last updated: 
Wednesday, March 3, 2021

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