Vaccine trials could lead To a mix-and-match system

HEALTH officials remain confident that the UK is on track to offer a Covid-19 vaccine to all adults by the end of July.

Many health boards in Wales are starting to invite people aged under 40 to come and get their vaccination, and more than half the adult population here have received the first vaccine.

Across the UK as a whole, more than 40 million doses of vaccines have been delivered, of which more than 32 million are first doses.

The UK also met its target to offer a Covid-19 vaccine to everyone in the top nine priority groups ahead of the April 15 deadline.

In addition to the successes of the roll-out programme, a study looking at whether the Oxfordastrazeneca and Pfizer coronavirus vaccines can be safely mixed for the first and second doses will also be expanded to include two additional jabs.

Researchers running the Com-cov study, launched in February to investigate alternating doses of the first two jabs to be rolled out across the UK, have announced that the programme will be extended to include the Moderna and Novavax vaccines.

Led by the University of Oxford, the extra study will seek to recruit adults aged over 50 who have received their first vaccination in the past eight to 12 weeks.

Matthew Snape, associate professor in paediatrics and vaccinology at the University of Oxford, who is chief investigator on the trial said: “The focus of both this and the original Com-cov study is to explore whether the multiple Covid-19 vaccines that are available can be used more flexibly, with different vaccines being used for the first and second dose.

“If we can show that these mixed schedules generate an immune response that is as good as the standard schedules, and without a significant increase in the vaccine reactions, this will potentially allow more people to complete their Covid-19 immunisation course more rapidly.

“This would also create resilience within the system in the event of a shortfall in availability of any of the vaccines in use.”

The researchers will study any adverse reactions and the immune system responses to these new combinations of vaccines.

If the study shows promising results, the MHRA and Joint Committee on Vaccination and Immunisation would formally assess the safety and efficacy of any new vaccination regimen before it is rolled out to patients.

Prof Snape said he hoped the results of the second part of the study would be available in June or July, with the first part expected to report results next month.

Professor Jeremy Brown, a member of the Joint Committee of Vaccination and Immunisation, said people would eventually “have to” mix Covid19 jabs.

He told BBC Radio 4’s Today programme: “It’s practically going to have to be that way because, once you’ve completed a course of, say, the Moderna or Pfizer or the Astrazeneca with two doses, in the future it’s going to be quite difficult to guarantee you get the same type of vaccine again.

“So there will be a mixand-match occurring just by the sort of practicalities of doing a third or fourth vaccination over the next few years...

“Getting data on that is important so there are trials at the moment about the immunological responses to the mixedvaccine combinations.”

Here is what vaccine you can expect to get in Wales and how effective each one is:

PFIZER Where it is being distributed?

All health boards in Wales are using the Pfizer vaccine.

Hywel Dda University Health Board says it aims to complete all second Pfizer vaccine doses by the end of this week.

What is its effectiveness?

The clinical trial data shows it is around 95% effective.

New research in Israel, which has predominately used the vaccine, had found that the variant first detected in South Africa may evade the vaccine, but it is extremely rare.

Any concerns?

Concerns were raised at the start about how quickly the vaccine had been developed – it was the first to be approved in the UK.

The vaccine was trialled on a large number of volunteers – about 40,000 – before being given approval.

All of the work and findings are checked and verified independently.

The Covid vaccine trials happened at breakneck speed, but they didn’t skip any steps. They were able to move faster because so many people were involved and other projects were put aside.

Approval is only given in the UK if the regulator is happy that a vaccine is safe and effective.

Checks continue after approval to make sure there are no further side effects or long-term risks.

ASTRAZENECA Where it is being distributed?

All health boards in Wales are also distributing the Astrazeneca vaccine.

In its latest newsletter, Swansea Bay University Health Board said they are putting on extra clinics to use doses of the Oxfordastrazeneca vaccine left over after people missed their appointments.

They say that anyone aged 18 to 29 will be offered an alternative to the Oxford-astrazeneca vaccine, but that anyone who received it as a first dose should have their second dose as planned.

What is its effectiveness?

Astrazeneca said that the latest results demonstrated vaccine efficacy of 76% after a first dose, with protection maintained to the second dose.

With an interval of 12 weeks or more, vaccine efficacy increased to 82% after the second dose.

Any concerns?

Concerns have been raised about a link between the vaccine and rare blood clots. However it appears to be very rare. Out of 20m vaccinations in the UK there have only been 79 blood clots and 19 deaths, although it has not been established what the cause was in every case.

This is a lower risk of blood clotting than with Covid itself.

The 79 cases occurred in 51 women and 28 men, aged from 18 to 79. Of the 19 who died, three were under the age of 30, the MHRA said.

Last week, European regulators said the clots they had seen were of a rare type that occurs together with low blood platelets, one that seems to occur more in younger people.

The European Medicines Agency (EMA) stressed that the benefits

‘‘ If we can show that these mixed schedules generate an immune response that is as good as the standard schedules, and without a significant increase in the vaccine reactions, this will potentially allow more people to complete their Covid-19 immunisation course more rapidly - Matthew Snape, associate professor in paediatrics and vaccinology at the University of Oxford

of receiving the vaccine outweigh the risks for most people.

But several countries have imposed guidelines on who can receive the vaccine; Britain recommended that people under 30 be offered alternatives.

The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK issued a statement saying the benefits of vaccination continue to outweigh any risks but the MHRA advises careful consideration be given to people who are at higher risk of specific types of blood clots because of their medical condition.

Dr Richard Evans, executive medical director, Swansea Bay University Health Board, said: “The UK’S Medicine Healthcare and Regulatory Products Agency (MHRA) has put out new advice following the possibility of a very rare blood clot being linked to the Oxfordastrazeneca vaccine.

“According to the MHRA, the risk of this side effect is very small, about four in one million, to those who receive the vaccine.

“More than 20 million doses of this vaccine have been given in the UK so far, with 79 reported cases of these unusual blood clots, which is an occurrence of 0.000395%.

“While you may be concerned about what you are hearing in the news, the MHRA has made clear that the benefits of vaccination greatly outweigh the risks, and this type of ‘course correction’ is common in vaccination schemes.

“But patient and product information will be updated to make sure everyone is aware of this very rare side effect along with other potential side effects.”

MODERNA Where it is being distributed?

Wales was the first place in the UK to roll out this vaccine, and a 24-year-old carer from Ammanford became the first person to receive the Moderna jab this month.

Elle Taylor got the vaccine at the West Wales General Hospital in Carmarthen on April 7.

Supplies arrived in Wales earlier this month, with 5,000 doses being sent to vaccination centres in the Hywel Dda University Health Board area.

The UK Government has bought 17 million doses, enough to vaccinate about 8.5 million people.

It comes after UK regulators said that people under the age of 30 should be offered an alternative to the Astrazeneca vaccine, saying there was a possible link between the jab and “extremely rare” blood clots.

This means people aged 18 to 29 who are offered the jab will be offered the Pfizer or Moderna jab until other vaccines are approved for use.

What is its effectiveness?

It was ruled safe and effective by the Medicines and Healthcare Products Regulatory Agency (MHRA) in January after stringent trials.

The company behind the vaccine has already said it is effective against both the Kent variant and the South Africa variant of the virus, which both spread faster and could be more deadly.

Studies have found that the efficacy against the disease is 94.1% and efficacy against severe Covid19 is 100%.

The results are based on more than 30,000 people in the UK who took part in the trial from a wide range of age groups and ethnic backgrounds.

Two doses were given 28 days apart so researchers could evaluate safety and any reaction to the vaccine.

Moderna also released data relating to severe cases.

All 30 severe cases occurred in the placebo group and none in the group which had received the vaccine, known as MRNA-1273.

Any concerns?

Moderna said the vaccine was generally well tolerated, with no serious safety concerns identified.

Severe events after the first dose included injection-site pain, and after the second dose included fatigue, myalgia (muscle pain), arthralgia (joint pain), headache, other pain and redness at the injection site.

But these were generally shortlived.

The jab needs to be stored at -25C to -15 C, and once it has been thawed it can be stored at 2C to 8 C for up to 30 days.

The minimum interval between first and second dose of the Moderna vaccine is 28 days.

And patients who receive the Moderna jab will need to wait at the vaccination centre and be observed for a period of 15 minutes after they receive the vaccine.

JOHNSON & JOHNSON Where it is being distributed?

This vaccine has not arrived in the UK yet, but in America there are recommendations for it being put on “pause” as investigations are carried out into reports of potentially dangerous rare blood clots.

The Johnson & Johnson vaccine (also known as the Janssen vaccine) uses the same technology as the Astrazeneca vaccine.

Both use an engineered adenovirus that is modified to mimic Sars-cov-2 but not to multiply in the body.

What is its effectiveness?

The J&J vaccine received emergency use authorisation from the FDA in late February, with hopes that its single dose and relatively simple storage requirements would speed up vaccination.

For severe disease, which includes people sick enough with Covid-19 to require medical intervention, the efficacy was 72% in trials in the US and 57% in South Africa, where a different variant is circulating.

Any concerns?

In America, the Centres for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) issued a joint statement saying they were investigating clots in six women that occurred six to 13 days after vaccination.

The clots were observed in the sinuses of the brain along with reduced platelet counts, making the usual treatment for blood clots, the blood thinner heparin, potentially “dangerous”.

More than 6.8 million doses of the J&J vaccine have been administered in the US, the vast majority with no or mild side effects.

US federal distribution channels, including mass vaccination sites, will pause the use of the J&J vaccine, and states and other providers are expected to follow.