What are the benefits of mixing and matching COVID-19 booster vaccines?

With cases of COVID-19 rising in the UK, the push to get everyone vaccinated is getting increasingly urgent. So far, more than 10 million people have received their third jab, with most being offered either Pfizer or Moderna for their booster. This means some people may receive a different vaccine from the one they had for their first two doses. But is this safe - and are there any advantages to mixing and matching vaccines?

The UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), has approved the Pfizer-BioNTech, Moderna and Oxford-AstraZeneca vaccines for use as a booster.

However, the UK's Joint Committee on Vaccination and Immunisation (JCVI) has decided to only use the two mRNA vaccines - Pfizer and Moderna - for third doses for most people, as they have slightly fewer side effects. This means someone who had an AstraZeneca vaccine for doses one and two, may be given a different one for their third.

Safe and effective

William Schaffner, a professor of preventive medicine at Vanderbilt University, says mixing and matching for booster jabs is becoming more common for two reasons. "The most important reason is that mixing offers advantages in enhanced immune response and, therefore, anticipated enhanced protection. The immune response after mixing is often higher than after matching," he says.

"There is a relatively small advantage to mixing the two mRNA vaccines (Pfizer and Moderna). However, there is substantial enhanced immunogenicity - a measure of how well a vaccine works - when the vector-based Johnson & Johnson vaccine (similar to the AstraZeneca vaccine) is followed by an mRNA vaccine."

The second reason is convenience. Mixing COVID-19 vaccines is emerging as a good way to get people the protection they need when faced with unpredictable supplies. "The individual may find that their most convenient vaccine provider has a vaccine different from the individual's first dose - just easier to mix rather than to match," says Schaffner.

Why mixing vaccines can trigger a stronger immune response

Multiple studies have shown that mixing and matching COVID-19 jabs isn't just safe - it can be more effective than having the same vaccine for each dose.

"Research and global real-time data have shown mixing and matching as an approach for COVID-19 vaccination is safe," says Rodney E. Rohde, a professor of clinical laboratory science and an infectious disease specialist at Texas State University. "In some cases, it can even be more effective than not mixing. It can show a very strong 'boost' effect."

In other words, mixing and matching vaccines can produce a stronger antibody response than sticking with the same vaccine for all doses. The exact reason why combining vaccines might improve efficacy is unknown, but we do know that vaccines present the same information in different ways.

For example, vector-based vaccines like AstraZeneca use a modified version of a virus that is different from the virus being targeted, in order to present part of the spike protein from the surface of SARS-CoV-2 - the virus that causes COVID-19 - to our immune systems. Messenger RNA (mRNA) vaccines, like the Pfizer and Moderna COVID-19 vaccines, teach cells how to make a similar protein that triggers an immune response if someone gets infected.

It is thought that when combined, these differences might kick start different parts of the immune system or trigger a stronger immune response. This may make immunity last longer too.

In October, a study by Umeå University in Sweden showed a 67% lower risk of infection for the combination of the AstraZeneca vaccine followed by the Pfizer jab, compared to people who hadn't been vaccinated. This compared to a 50% reduction among people who had the Oxford jab twice.

Meanwhile, having the AstraZeneca vaccine followed by Moderna - another mRNA vaccine - cut the risk of infection even more sharply, by 79%.

Stronger antibody response

Other studies have found that mixing COVID-19 vaccines can produce a stronger immune response. A Spanish study published in July 2021 reported that people who initially received the AstraZeneca vaccine experienced a significant increase to their antiviral immunity when given a second dose of the Pfizer vaccine.

"A National Institutes of Health study tested nine different combinations of Johnson & Johnson, Moderna and Pfizer vaccines given to 458 participants and found that mixing was safe and highly effective," says Rohde.

"The concise story of this study shows that receiving a booster shot greatly increased the circulating number of antibodies including neutralising antibodies - molecules that bind to the virus and stop it from infecting cells - against SARS-CoV-2."

Interestingly, in individuals who got a different booster than their original vaccine series, neutralising-antibody levels increased 6.2- to 76-fold, depending on which vaccine combination they received. People who received the same booster as their original vaccine saw their neutralising-antibody levels increase between 4.2- and 20-fold.

Should vulnerable people mix and match COVID-19 vaccines?

The priority for everyone, especially vulnerable people, is to be fully vaccinated against COVID-19. People who are eligible for their third jab are being encouraged to get it as soon as possible. Although millions of people have received their booster, around 30% of over-80s and 40% of over-50s in England are yet to do so.

"The most important thing is for people to be vaccinated, period," says Rohde. "Those initial vaccines are critical to help reduce the ease at which SARS-CoV-2 can find a host. The more we can enhance immunity in the global population, typically the more we can reduce the virus from easily mutating.

"We may not stop it, but we can reduce the danger and slow down the mutation. Immuno-compromised and others in high-risk work groups - for example, healthcare workers - are among those most strongly recommended to get vaccinated, when the time comes, to be boosted."

Who can get a COVID-19 booster jab?

Currently, booster vaccine doses are available on the NHS for people most at risk from COVID-19 who have had a second dose of a vaccine at least six months ago. This includes people aged 50 and over, those in care homes, frontline health and social care workers and people aged 16 and over with a health condition that puts them at high risk.

On 8th November 2021, the regulations changed to allow people to book a booster online up to a month in advance. You will still need to wait until at least six months from your second dose to have your booster, but you can book your appointment from five months after your second dose.

People aged 16 and over who are a main carer for someone at high risk, and those aged 16 and over who live with someone immuno-compromised, can also get a third jab. People who are pregnant and in one of the eligible groups can also get a booster dose.

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