A major UK study examining whether Covid vaccines can be safely mixed with different types of jabs for the first and second doses is to be expanded.
Researchers running the Com-Cov study, launched in February to investigate alternating doses of the Oxford/AstraZeneca and Pfizer vaccines for the first and second doses, will now include a shot of the Moderna or Novavax vaccines.
The study is examining whether mixing vaccines may give broader, longer-lasting immunity against the virus and new variants, and offer more flexibility in the administration of vaccines.
Led by the University of Oxford, the study will seek to recruit adults aged over 50 who have received their first vaccination in the past eight to 12 weeks.
Matthew Snape, an 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 the availability of any of the vaccines in use.”
The volunteers, who will have received either the Oxford/AstraZeneca or Pfizer/BioNTech vaccine, will be randomly allocated to receive either the same vaccine for their second dose or a dose of the jabs produced by Moderna or Novavax.
The Moderna jab has started being rolled out across the UK, and the Novavax jab manufactured by GlaxoSmithKline (GSK) is under review by the Medicines and Healthcare products Regulatory Agency (MHRA).
The six new arms of the trial will each recruit 175 candidates, adding 1,050 recruits to the programme. The researchers will study any adverse reactions and the immune system responses to these new combinations of vaccines.
What are the most common side-effects from the Covid vaccines?
According to Public Health England, most side-effects from the Covid vaccines – Pfizer/BioNTech and Oxford/AstraZeneca – are mild and short-lived. These include soreness where the jab was given, feeling tired or achy and headaches. Uncommon side-effects include having swollen lymph nodes.
Why do the common side-effects occur?
“The sore arm can be either due to the trauma of the needle in the muscle, or local inflammation in the muscle probably because of the chemicals in the injection,” said Prof Robert Read, head of clinical and experimental sciences within medicine at the University of Southampton and director of the NIHR Southampton Biomedical Research Centre.
“The other common side-effects – the muscle aches, flu-like illness and fatigue – are probably due to generalised activation of the immune system caused by the vaccine. What this means is that the white blood cells that are stimulated by the vaccine to make antibodies themselves have to secrete chemicals called cytokines, interferons and chemokines, which function to send messages from cell to cell to become activated.”
Are blood clots a side-effect of the vaccines?
The Oxford/AstraZeneca jab has been linked to a small but concerning number of reports of blood clots combined with low platelet counts (platelets are cell fragments in our blood that help it to clot). Distribution of the Johnson & Johnson vaccine has been "paused" in the US while scientists investigate six incidences of a rare type of blood clot.
These include a rare clot in the brain called cerebral venous sinus thrombosis (CVST). In an unvaccinated population, upper estimates suggest there may be 15 to 16 cases per million people per year.
The Medicines and Healthcare products Regulatory Agency (MHRA) said recipients of the Oxford/AstraZeneca jab should look out for new headaches, blurred vision, confusion or seizures that occur four days or more after vaccination. The MHRA also flagged shortness of breath, chest pain, abdominal pain, leg swelling and unusual skin bruising as reasons to seek medical advice.
Up to and including 31 March, the MHRA said it received 79 reports of cases of blood clots combined with low platelets, including 19 deaths, following more than 20m doses of the Oxford/AstraZeneca jab. That equates to about four cases for every million vaccinated individuals.
Two cases of blood clots with a low platelet count have also been reported among recipients of the Pfizer/BioNTech jab. The European Medicines Agency is also examining three cases of venous thromboembolism blood clots involving the Johnson & Johnson jab.
The MHRA says blood clots combined with low platelets can occur naturally in unvaccinated people as well as in those who have caught Covid, and that while evidence of a link with the Oxford/AstraZeneca vaccine has become stronger, more research is needed.
Nicola Davis Science correspondent
If the study shows promising results, the MHRA and Joint Committee on Vaccination and Immunisation (JCVI) would formally assess the safety and efficacy of any new vaccination regimen before it is rolled out to patients.
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.
He told a press briefing: “What I’m hoping is that we won’t rule out any combinations. That’s how we need to look at it – are there any combinations we shouldn’t be giving because they don’t generate a good immune response, and I’m hoping that won’t be the case.
“And that will give us lots of flexibility, not just in the UK, not just in Europe where we’re looking about restricting uses of some vaccines for some age groups, but across the world, where we have, perhaps, a little bit more intermittent supply of vaccines, not as reliable.”
Prof Jeremy Brown, a member of the JCVI, said people would eventually have to mix Covid-19 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.”
