COVID-19

Q and A on the AstraZeneca/Oxford COVID-19 vaccine (AZD1222)

British Society for Immunology

Please note that the answers to the following questions apply in relation to the AstraZeneca/Oxford COVID-19 vaccine, and some answers will be different for other COVID-19 vaccines. 

Rollout

Who is eligible to receive the vaccine?

The Joint Committee on Vaccination and Immunisation (JCVI) has prioritised people for vaccination based on their risk of serious COVID-19 disease after SARS-CoV-2 infection.  The priority order, confirmed on 2nd December and subject to logistical challenges in rollout, is as follows:

  1. Residents in a care home for older adults and their carers
  2. All those 80 years of age and over; frontline health and social care workers
  3. All those 75 years of age and over
  4. All those 70 years of age and over; clinically extremely vulnerable individuals
  5. All those 65 years of age and over
  6. All individuals aged 16 years to 64 years with underlying health conditions which put them at higher risk of serious disease and mortality
  7. All those 60 years of age and over
  8. All those 55 years of age and over
  9. All those 50 years of age and over

As more vaccine becomes available, it will be rolled out to those in each descending group.

Why are older people being prioritised over younger people who are out of the house working?

The priorities are based on reducing risk of harm.  The immune system in older people differs from that of younger people and whilst the younger, working population are just as likely to become infected they are much, much less likely to become severely ill. An older person becoming infected with SARS-CoV-2 is more likely to result in severe COVID-19 disease and require hospitalisation.  The biggest risk of dying from COVID-19 comes with age, even more so than underlying conditions such as cardiovascular disease or diabetes, for example, or being male or being in BAME groups.  With each 20 year increase in age the risk of dying from COVID-19 increases by approximately 10 times.  When a vaccine has been shown to be effective in preventing disease in older people, then they should be the first to receive it as they are most at risk.

Do I need to get the vaccine if I have contracted COVID-19 and recovered?

Yes.  There is a lot of uncertainty about how much immunity a person gains after natural infection.  The levels of immunity that we can measure so far show a lot of individual variation – some people have very few antibodies after infection, but these antibodies can be boosted by vaccination.  We can’t assume that everyone who has had COVID-19 would have enough immunity to protect them. It is likely that, in a significant proportion of the population, the vaccine will induce more effective and longer lasting immunity than that induced by infection. Hence it is recommended that everyone take the vaccine so that, if your immunity after disease is absent or low, it can be boosted.

Why should a young person take the vaccine when the risk of COVID-19 mortality is so low?

There is a huge variability in the symptoms and severity of COVID-19 disease between different people; from an infection with SARS-CoV-2 that doesn’t have any symptoms (asymptomatic infection) to severe COVID-19 disease resulting in hospitalisation and in some cases death.  While younger people are usually at the less severe end of the spectrum this does not mean that the illness is not harmful to their health.  In fact, there are many instances of long COVID that have blighted the lives of young people. 

In addition, although we don’t yet have a lot of evidence to support this, having the vaccine might stop you being able to be part of the chain of infection that spreads the virus.  So, an added benefit might be to help reduce spread of the virus for everybody.

There is COVID-19 at my child’s school. Why aren’t my children being given the vaccine?

Initial vaccine testing was not done on children.  Children are at extremely low risk of becoming severely ill with COVID-19 – they are at higher risk of being involved in a serious traffic accident than they are of ending up in hospital with COVID-19. So the benefits of vaccinating children are not yet clear. If the vaccine stops people from passing the infection to others, then vaccinating children in order to stop the spread of the virus will make a lot of sense.

Safety

Does the AstraZeneca/Oxford vaccine being developed so quickly mean that it is less safe than other vaccines?

No, it doesn’t.  The reasons that this was developed so quickly do not include cutting corners on safety.  There are a few reasons that enabled the speed in 2020:

  1. Technology. This viral vector vaccine (in common with many of the approaches used for the other vaccine candidates) could be rapidly deployed for development and testing once the SARS-CoV-2 genetic sequence became known, but this was actually done on the back of almost ten years prior research using this method of producing vaccines.
  2. Scientists.  A LOT of scientists contributed to this, working extra long hours to make it work and to assess the results.
  3. Money.  Normally raising money to develop a vaccine takes a long time.  At each stage you have to stop and apply for more funding to carry out the next stage.  Funding applications take a year or more.  In 2020 for SARS-CoV-2, rapid investment of a lot of taxpayers’ money in many countries meant there weren’t the normal financial obstacles.
  4. Environment. Sometimes you can develop a vaccine but can’t test it until there is an epidemic in progress.  There was no problem in this regard.
  5. Luck.  Sometimes the target that is picked for vaccine studies, which is usually something seen on the outside of the virus, is not a good candidate for raising an immune response.  The S protein target on SARS-CoV-2 that most vaccine companies picked to work with turns out to be an excellent target for activating the immune response.
  6. Volunteer test subjects.  Last but definitely not least.  Tens of thousands of volunteers took part in the safety trials and the randomised control trials so recruiting volunteers was not an issue as it may be under normal circumstances.
  7. Testing. Normally the various phases of safety testing happen sequentially, often because of financial restraints, in this case safety testing happened concurrently.

Are there any side effects from the vaccine?

Yes, but these are generally mild. As with all vaccines, because you are stimulating the immune system you may experience some mild flu-like symptoms, but these are temporary.  The most common reactions are fatigue, headache and pain at the injection site.  Some people might also get chills, joint pain or fever. 

Should people with allergies take the vaccine?

Most people with allergies can have the vaccine. For example, some allergies, such as hay fever, are mild and do not pose a risk.  The MHRA recommends that people with a history of anaphylaxis to food, an identified drug or vaccine, or an insect sting CAN receive any COVID-19 vaccine, as long as they are not known to be allergic to any component of the vaccine. The vaccine should not be given to people who have a history of immediate-onset anaphylaxis to any of the vaccine’s components.  If you carry an EpiPen in case of allergic reaction, you have a history of immediate-onset anaphylaxis and so should discuss this with your doctor, nurse or pharmacist before getting the vaccine.  People are asked to remain at the vaccination centre for a short period of time after receiving their vaccination so that the healthcare professionals can check there is no immediate adverse response to the vaccine.

Who should not get the vaccine? (I’m immunocompromised/pregnant etc.)

The AstraZeneca/Oxford COVID-19 vaccine has not yet been tested on pregnant women or children so these groups should only be vaccinated where the benefit of vaccination is thought to outweigh any potential harm, and should be discussed on an individual basis. Similar adenoviral vectored vaccines have been used safely in children and pregnant women for other infectious diseases (e.g. malaria and Ebola).

Immunocompromised people are at high risk so should get the vaccine. Although the AstraZeneca/Oxford COVID-19 vaccine contains a live adenovirus, it has been modified so that the virus is unable to replicate in humans, so unlike other ‘live’ vaccines, it is safe for people with compromised immune systems.  However, because their immune systems may not be able to make a response to vaccine they should still take other precautions against the disease.

Who was the AstraZeneca/Oxford COVID-19 vaccine tested on?

In the phase 3 clinical trial, half the volunteers had the COVID-19 vaccine and the rest were given a MenACWY (meningitis) vaccine, or saline solution, as control. Volunteers were from Brazil, and UK, other trials are continuing in South Africa and USA. 

In the data published so far, from the UK and Brazil, there were 5,807 COVID-19 vaccine recipients and 5829 in the control group.  Of the COVID-19 vaccine recipients, 88% were aged between 18 and 55, 12% were aged over 55.  17% were BAME, 39% were male.  People characterised as high risk due to underlying conditions (e.g. cardiovascular disease; diabetes; respiratory disease) or due to high risk occupations were included.

Are there risks that might have been missed in the trials, but will become apparent in the longer term?

All known risks have been checked, but there may be unknown risks.  Reactions to vaccines usually happen very soon after vaccination – if you have the vaccine, you are asked to wait at the vaccination centre for a few minutes as a precaution.  All the initial phase 1 safety trial volunteers have been followed up for at least 7 months and no major concerns have been raised.  Safety monitoring, known as pharmacovigilance, is to be continued for 2 years after the vaccine is released;  in the UK, this is carried out by the MHRA.

How are long term side effects tested/monitored?

Safety monitoring is to be continued for 2 years after the vaccine is released. There is a system in place (known as the yellow card system; https://yellowcard.mhra.gov.uk/) to monitor and report adverse events immediately in a process known as pharmacovigilance. In the UK, this is carried out by the MHRA.

Effectiveness

Does immunity from the vaccine last longer than immunity after getting COVID-19?

We do not know the answer to this question yet because people have only been followed up for a maximum of 7 months after vaccination so far.  We suspect that in some cases (e.g. mild or asymptomatic infection), the immunity elicited by the vaccine would be better than that elicited by the natural infection, but we do not know for sure. But, from the concentrations of antibodies induced by the vaccine, and the rate at which these antibodies decline over time, it is looking very promising that immunity induced by the vaccine will last at least as long as the immunity induced by infection and in all likelihood it will last much longer.

Do I still need to wear a mask or observe social distancing after receiving the vaccine?

Yes.  We know the vaccine can protect people from getting sick from the disease COVID-19 that is caused by the viral infection.  However, we do not yet know if being vaccinated will stop you from getting the viral infection, so you could be an asymptomatic carrier who could pass the infection onto others who may be vulnerable.

Also, you will not be protected against the disease until at least three weeks after your first dose and you will not be fully protected until three weeks after your second dose.

Other

How do viral vector vaccines, such as the AstraZeneca/Oxford vaccine, work?

This type of vaccine uses an unrelated harmless virus (the viral vector) to deliver SARS-CoV-2 genetic material into the body. When administered, our cells use the genetic material to produce a specific viral protein, which is recognised by our immune system and triggers a response. This response builds immune memory, so your body can fight off the virus in the future.

Are the changes to the times between the first and second doses of the vaccine safe? Will it cause the virus to mutate?

The British Society for Immunology has issued a statement laying out our thoughts on this complex issue.  Although we would prefer the original dosing schedules tested in the trials to be used clinically, we recognise that with the extremely high current case numbers, a pragmatic approach in the short-term is needed, and accept the rationale for the change in dosing schedule to a 12-week gap between first and second dose recommended by the Joint Committee on Vaccination and Immunisation (JCVI).  There is evidence for the AstraZeneca/Oxford vaccine that a 12 week interval may be better than 4 weeks.  It is important to emphasise that people do need to go back to get their second dose to receive full protection.,

Modelling data has shown that vaccination has by far the largest chance of reducing the disease burden and death rate compared with other measures. Any risks from actions taken now must be balanced against risks of actions not taken. Concerns over hypothetical consequences of putting the virus under pressure to mutate from non-sterilising vaccine regimes have to be balanced against a view of what we would face through the virus spreading at the current rate in our communities.

Will the vaccine be effective against different variants of the SARS-CoV-2 virus?

The human immune system is diverse and dynamic so we think it will, but we don’t yet know this for a fact in all variants. We will need to monitor emerging virus variants and continually check (in the lab) whether serum from vaccinated people can neutralise them. So far there is no evidence that the UK variant can escape from antibodies made in response to the old variant.  There is some evidence that another variant might be able to escape, and studies are ongoing to investigate this further.  If we find any significant reduction in neutralisation of variant viruses, we may need to subtly tweak the vaccine to induce a broader repertoire of neutralising antibodies.

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