COVID-19 vaccines

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. Most of the fatalities 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:

• Increasing age
• Male sex
• Underlying health conditions (clinically vulnerable)
• Clinically extremely vulnerable
• Being from a black, ethnic or minority group 
• Working in health and social care

More information about COVID-19 disease, including the global impact of the pandemic see: Coronavirus (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 350 vaccines are in various stages of development, and some of these use similar technologies to vaccines already in use, whilst others involve newer approaches. 

Although clinical trials were 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, three vaccines are currently in use, although six have been approved by the Medicines and Healthcare products Regulatory Agency (MHRA). These include the BNT162b2 vaccine, developed by Pfizer and BioNTech, the ChAdOx1 nCoV-19 (AZD1222) vaccine, developed by the University of Oxford and AstraZeneca, and the mRNA-1273 vaccine developed by Moderna. For more information about how vaccines are licensed, see How vaccines are tested, licensed and monitored.

The aim of the COVID-19 vaccination programme is to protect those who are most at risk of becoming seriously ill with COVID-19. Recommendations for the UK vaccination programme from the UK Joint Committee on Vaccination and Immunisation (JCVI) include: 

Adults: 

• All adults in the UK are now eligible for first, second and booster doses. In England, Northern Ireland and Scotland, all adults over 18 can book their booster dose. In Wales, invitations to book booster doses will be sent out from the local health boards. 
• The gap between the second dose and booster dose has been reduced to a minimum of three months (before, this was six months).
• Spring boosters are now available for adults aged 75 years or older, residents in care homes and individuals with weakened immune systems.

Children:

• Two doses are now recommended for all children aged 5-17 years. Previously, COVID-19 vaccines were only available to children aged 12 and up, or those aged 5-11 years who were deemed to be in a clinical risk group. Booster doses are available to all individuals aged 16+ and children aged 12-15 if they are clinically at risk or live with an immunosuppressed individual. 

Severely Immunosuppressed Individuals:

• Fourth doses as a booster have been recommended for severely immunosuppressed individuals, a minimum of three months after their third dose.

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. Fourth doses have been recommended for severely immunosuppressed individuals in the UK. 

Pregnancy and breastfeeding

The Pfizer-BioNTech and Moderna vaccines are recommended for use in pregnant women, as there is more information about these vaccines being given to this group. Vaccination against COVID-19 is recommended for pregnant women, as they are at a higher risk of developing severe complications from COVID-19. There is also evidence of increased risk of premature birth or miscarriage if COVID-19 is contracted during pregnancy. The best way to protect the mother and baby from these risks is to receive two doses of a COVID-19 vaccine. 

The JCVI recommended that women who are breastfeeding may be offered two doses of COVID-19 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. As of November 2021, all children aged 12-17 are eligible for a second dose three months after their first dose. For children in school, they will be offered the vaccine in their school setting. If a child misses their vaccine at school, they can receive it through a COVID-19 vaccine clinic. Some children aged under 16 with complex medical conditions or those who live with someone who is immunocompromised may be advised to receive two doses of a COVID-19 vaccine. Clinical trials are underway to increase evidence for use of COVID-19 vaccines in younger children.

Who can’t have the vaccines? (Contraindications)

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 COVID-19 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 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.

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.

Click here for an accessible text version of this infographic

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 transcribe 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.