Scientists are investigating the optimal coronavirus vaccine that could be administered as a third booster jab.
The UK has three approved vaccines in its immunisation arsenal against the pandemic – Pfizer-BioNTech, University of Oxford-AstraZeneca and Moderna.
The jabs' roll-out has been unprecedented, with more than 36 million people having received their first dose alone. As a result, coronavirus-related deaths have plummeted from the 1,325 peak on 8 January to seven fatalities on 18 May.
With many expecting the coronavirus to become a seasonal infection, a third booster jab may be required to ward off a dreaded third wave during the UK's winter, particularly if vaccine-induced immunity wanes or immunisation-escaping variants emerge.
The government is therefore funding a £19.3m ($27.3m) study into the effects of administering a single shot of seven vaccines – some of which have not been signed off in the UK – at various doses in people who have already received two Pfizer-BioNTech or Oxford-AstraZeneca jabs.
"We will do everything we can to future-proof this country from pandemics and other threats to our health security, and the data from this world-first clinical trial will help shape the plans for our booster programme later this year," said health secretary Matt Hancock.
"I urge everyone who has had both doses of a COVID-19 [the disease caused by the coronavirus] vaccine, and is eligible, to sign up for this study and play a part in protecting the most vulnerable people in this country and around the world for months and years to come."
Preliminary results of the study – led by the University Hospital Southampton NHS Foundation Trust – will inform the Joint Committee on Vaccination and Immunisation (JCVI) as to whether a booster is required and, if so, which vaccine may be the most appropriate.
The JCVI is expected to receive these initial results in September.
In the meantime, the scientists behind the trial are hoping to recruit close to 2,900 people aged 30 or over at 18 sites across Britain. People who had the Moderna jab are not eligible due to it only being rolled out relatively recently.
Some of the participants will be given one of the UK's three approved vaccines or another jab that is under assessment – Novavax, Janseen, Valneva or Curevac – as their third dose. This will be administered at least 10 to 12 weeks after they received the second vaccine in the standard two-dose regimen.
The scientists are specifically assessing how the different jabs' side effects vary when given as a booster. These adverse events will be compared against that of the meningococcal vaccine, which some of the participants will receive as a control jab.
Prior to its approval, the Oxford-AstraZeneca vaccine was tested against the meningococcal jab, which wards off bacteria that can cause meningitis.
"We're expecting all [of the seven boosters] to work immunologically, but some may have more side effects based on what [vaccine] you've already had," said lead investigator Professor Saul Faust.
The study is too small to pick up on very rare side effects, like the unusual blood clots that have emerged in a small minority of people after the Oxford-AstraZeneca jab. Post-vaccine surveillance therefore continues to be important, added the scientists.
While all the booster doses will be compared against the meningococcal jab, some will also be judged against themselves when given at a full dose versus a half dose.
"Half doses are being given [to potentially help] vaccine supply," said Professor Faust. Halving doses means twice as many people can be immunised worldwide.
A half dose may also reduce side effects or even bring about a more potent immune response.
While it may sound counterintuitive, the Oxford-AstraZeneca vaccine was found to be 90% effective when given as a half dose followed by a full dose. This is compared to 62% when both jabs were full dose.
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As well as monitoring for side effects, the participants will have their immune response measured via blood samples drawn 28, 84, 308 and 365 days after the third jab.
Their immune cells will be assessed in the laboratory against the original variant of the coronavirus that is thought to have emerged in Wuhan, China, at the end of 2019.
The effects of the boosters will also be tested against three "variants of concern" – those which were identified in Kent, India and South Africa – as well as any others that may emerge.
The UK's three vaccines were developed according to the Wuhan variant. The emergence of new variants has left many concerned mutated viruses may spread more readily, cause more severe disease or evade vaccines.
Experts are unanimously optimistic the jabs will be at least somewhat effective against new variants.
Nevertheless, some are concerned about so-called "original antigenic sin" – the phenomenon whereby the development of immunity against pathogens is shaped by the first exposure to a related pathogen.
"Your immune system is exposed to the Wuhan variant via the [coronavirus] vaccines," said co-study investigator Dr Matthew Snape, from the University of Oxford.
"Even if you change the vaccine to the South Africa variant, in some circumstances your immune system will still try and react to the original Wuhan variant."
Rather than tweaking the vaccines to match new variants, experts could try to induce a higher number of infection-fighting antibodies against the Wuhan variant, which may then give "some cross protection" against new mutations.
Nadhim Zahawi, minister for COVID-19 vaccine deployment, added: "Having taken part in a COVID-19 vaccine clinical trial myself, I would encourage everyone eligible to volunteer.
"It's a fantastic opportunity to get involved with such an historic initiative."
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