Mixing Covid jabs has good immune response, study finds


A mix-and-match approach to Covid vaccines – using different brands for first and second doses – appears to give good protection against the pandemic virus, a UK study has found.

The Com-Cov trial looked at the efficacy of either two doses of Pfizer, two of AstraZeneca, or one of them followed by the other.

All combinations worked well, priming the immune system.

This knowledge could offer flexibility for vaccine rollout, say experts.

The trial results also hint that people who have already received two doses of AstraZeneca vaccine could have a stronger immune response if they were given a different jab as a booster if recommended in the autumn.

The UK’s deputy chief medical officer, Prof Jonathan Van-Tam, said there was no reason to change the current successful same dose vaccine schedules in the UK, however, given vaccines were in good supply and saving lives.

But he says it might be something to look at in the future: “Mixing doses could provide us with even greater flexibility for a booster programme, while also supporting countries who have further to go with their vaccine rollouts, and who may be experiencing supply difficulties.”

Some countries are already using mixed doses. Spain and Germany are offering the Pfizer or Moderna mRNA vaccines as a second dose to younger people who have already received a first dose of the AstraZeneca vaccine, following concerns about rare but serious blood clots, rather than about efficacy.

Two doses are important to give the fullest protection and teach the body to make antibodies and T cells to block and kill Covid.

The Com-Cov study, which looked at giving the doses four weeks apart in 850 volunteers aged 50 and above, found:

  • AZ followed by Pfizer induced higher antibodies and T cell responses than Pfizer followed by AZ
  • Both of these mixes induced higher antibodies than two doses of AZ
  • The highest antibody response was seen after two doses of Pfizer, and the highest T cell response from AZ followed by Pfizer

Lead investigator Prof Matthew Snape, from the University of Oxford, said the findings did not undermine the UK policy of giving people the same jab twice: “We already know that both standard schedules are very effective against severe disease and hospitalisations, including against the Delta variant when given at eight to 12 weeks apart.”

He said the new results showed mixed dose schedules were also effective, even though the interval of four weeks studied was shorter than the eight to 12-week schedule most commonly used in the UK.

“This longer interval is known to result in a better immune response,” he added.

Mixed dose trial results for a 12-week jab interval will be available next month.

Autumn booster dose?

Meanwhile, another pre-print study, which also came out on Monday, suggests a third dose of AZ vaccine, given more than six months after the second, boosts the immune system.

But experts say it is too early to know if people will need a booster dose this year ahead of winter. It is unclear yet how much immunity might wane over time.

Prof Paul Hunter from the University of East Anglia said: “The big question at present is whether or not we will be being offered booster vaccines in the autumn. With the evidence available from this and other sources, I suspect that will be likely for those most at risk from the virus, either due to age or being clinically vulnerable.”

He suggested people who have had a first course of AstraZeneca might be offered the Pfizer vaccine in as a booster rather than a repeat AstraZeneca, while people who had a Pfizer first course may not need an autumn booster, based on the evidence from the Com-Cov trial.

The initial results of this mix and match vaccine trial are highly encouraging and throw up some interesting options for booster doses.

Mixing first and second doses of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines yielded strong immune responses. Indeed, every combination of dosing – Pfizer/Pfizer, AZ/Pfizer or Pfizer/AZ produced higher antibody and cellular responses than AZ/AZ.

Does this mean that two doses of AstraZeneca is somehow inferior? Not necessarily.

It is worth remembering that two doses of AZ are already proven to reduce the chances of being hospitalised with Covid by more than 90%.

So we know from real world evidence that the AZ vaccine is highly effective. The AZ vaccine is a ‘slow burner’, and immunity levels build over time, especially when the dosing period is stretched. Currently the gap between first and second doses is between eight and 12 weeks which should give a better immune response.

What this trial suggests is that for the third, booster doses, it may be preferable to give a different brand of vaccine than the one used for the first two shots.

But it’s also worth noting that mixing vaccines does produce more short-term side effects such as chills, headaches and muscle pain.

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