Mix and match coronavirus vaccine doses investigated by scientists
A clinical trial will investigate the safety and efficacy of alternating different coronavirus vaccine doses.
Scientists from the UK’s National Immunisation Schedule Evaluation Consortium (NISEC) are recruiting 820 adults over 50 to receive the Pfizer-BioNTech vaccine as a first dose, followed by the AstraZeneca-University of Oxford booster jab, and vice versa.
Outcomes will then be compared against those who received the same vaccine as part of the two-dose regimen, as per the existing immunisation protocol.
Dosing intervals will also be investigated, with some having the jabs four weeks apart and others with a 12-week gap.
Read more: Sputnik vaccine 91% effective against symptomatic coronavirus
Blood samples will be collected to measure the participants’ immune response against the coronavirus, including its newly-emerged variants.
Although unclear ahead of the results, some are optimistic alternating the doses may lead to a more potent immune response.
“Given the inevitable challenges of immunising large numbers of the population against COVID-19 [the disease caused by the coronavirus] and potential global supply constraints, there are definite advantages to having data that could support a more flexible immunisation programme, if needed and if approved by the medicines regulator,” said Professor Jonathan Van-Tam, England’s deputy chief medical officer and the study’s senior responsible officer.
“It is also even possible by combining vaccines, the immune response could be enhanced giving even higher antibody levels that last longer; unless this is evaluated in a clinical trial we just won’t know.
“This study will give us greater insight into how we can use vaccines to stay on top of this nasty disease.”
Read more: J&J’s one-dose vaccine 85% effective against severe COVID
Adults interested in taking part can sign up to the coronavirus vaccine research registry.
While the Moderna vaccine is also approved in the UK, the trial is only looking at the Pfizer-BioNTech and AstraZeneca-Oxford jabs, which are being more widely rolled-out.
Assuming more coronavirus vaccine candidates are given the green light, other jabs may be added to the investigation, according to the NISEC scientists.
Watch: Can you catch coronavirus twice?
While the approach may sound novel, it has been successful for other infections.
“Ebola vaccines used different vaccines for priming and boosting,” said chief investigator Professor Matthew Snape, from the University of Oxford. “It might well be preferable.”
The Pfizer-BioNTech and AstraZeneca-Oxford jabs are based on different technologies.
Nevertheless, they both make the immune system think the coronavirus has invaded the body, triggering a response.
The AstraZeneca-Oxford jab is based on a modified version of a chimpanzee adenovirus, which causes common cold-like symptoms.
Read more: Germany recommends over 65s bypass AstraZeneca coronavirus vaccine
“[When] getting the second dose, sometimes the immune response is focused on the carrier adenovirus, not the [coronavirus] spike protein,” said Professor Snape.
“So there might be some rationale to mixing it up.”
The coronavirus uses its spike protein to invade cells, with it being a target for many vaccines.
Dr Peter English, past chair of the British Medical Association’s public health medicine committee, agreed with the concept of so-called heterologous boosting.
“Examples include hepatitis B, where some people respond poorly to vaccination but better if a heterologous booster is given; and some of the candidate vaccines for a better tuberculosis vaccine,” he said.
“We have seen the [Russian coronavirus] Sputnik vaccine uses a form of heterologous boosting; it is a vector vaccine and the vector is different for the two doses.
“This seems to have been done partly out of concern the immune system might recognise the vector virus used, reducing the efficacy of the booster dose.”
Read more: 21 anaphylaxis cases to first Pfizer coronavirus jab out of 1.8 million jabs
The NISEC trial will also investigate whether a 12-week dosing interval is more or less effective than a four-week gap, with the government extending the time between jabs to increase the number of people getting the first vaccine.
“We have seen the AstraZeneca vaccine appears more effective with a longer prime-boost interval,” said Dr English. “This was no surprise to vaccinologists; it is to be expected.
“The short prime-boost interval in the initial vaccine trials was presumably chosen because the efficacy of vaccination after a single dose was not predicted to be as high as it has turned out to be; to provide better initial immunity, at the expense of longer term immunity.
“So that the [NISEC] trial is looking at different intervals is interesting and should yield some valuable data.”
Safety will also be monitored throughout the study.
As a precautionary measure, the UK’s vaccine regulator recommends anyone with a history of severe allergic reactions bypasses the Pfizer-BioNTech jab.
Speaking of the alternating dose approach, Professor Snape said: “Someone who had an allergic reaction to the first vaccine would potentially have the option of a second vaccine.”
The trial, which has received £7m ($9.5m) in government funding, is expected to complete recruitment by the end of February.
Preliminary results are due around June, however, the full study will last 13 months.
The alternating dose regimen will exist only within the trial, with the UK’s ongoing vaccination programme being unchanged.
Assuming promising results, the government may review its vaccine regimen, if recommended by the Joint Committee on Vaccination and Immunisation (JCVI), according to the NISEC scientists.
“This is a hugely important clinical trial that will provide us with more vital evidence on the safety of these vaccines when used in different ways,” said Nadhim Zahawi, minister for COVID-19 vaccine deployment.
“Nothing will be approved for use more widely than the study, or as part of our vaccine deployment programme, until researchers and the regulator are absolutely confident the approach is safe and effective.”
The NISEC scientists are recruiting participants across eight sites, including in London, Birmingham and Liverpool.
The team aims to enrol adults from a range of ethnic backgrounds. Those with pre-existing health conditions may also be eligible.
When asked why only over-50s can enrol, Professor Snape said: “We want the results to be relevant for people at greater risk of disease.
“Many over 70s [in the UK] are already immunised.
“We’re looking for a middle ground; who have some risk of disease but are not 21-year-olds.”
People who have tested positive for the coronavirus in the past are not eligible, however, those with protective antibodies following an asymptomatic infection can take part.
“This is a tremendously exciting study that will provide information vital to the roll out of vaccines in the UK and globally,” added Professor Snape.
“We call on those aged 50 years and above who have not yet received a COVID-19 vaccine to visit our website to find out more about the study and see if there is a study site near them.
“If we do show these vaccines can be used interchangeably in the same schedule this will greatly increase the flexibility of vaccine delivery and could provide clues as to how to increase the breadth of protection against new virus strains.”
Watch: What is long COVID?
