COVID-19 Vaccines

Mix and Match Immune Response of COVID Vaccines

The mix-and-match approach to COVID-19 vaccines by using different brands for first and second doses- appears to offer good protection against the pandemic virus, a study in the UK has found.

The Com-Cov trial looked at the efficacy of either two doses of AstraZeneca, two of Pfizer, or one of them followed by the other. All the combinations worked well, priming the immune system.

The knowledge could offer the flexibility for vaccine rollout as per the experts. The trial results hint that people who have received the two doses of the AstraZeneca vaccine may have a healthy immune response. If they were given a different vaccine as a boost if recommended in the autumn.

Prof Jonathan Van-Tam, the UK’s deputy chief medical officer said, “There was no reason to change the current successful dose vaccines schedules in the UK. However, vaccines were good in saving lives and supply.”

He also says it might be something to look at in the future. Mixing the doses could provide greater flexibility for a booster program, while it also helps to support countries who have to go further with their vaccine rollouts, and who may be experiencing difficulties related to supply.

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

About rare blood clots

Two doses of vaccine shots are essential as it provides the fullest protection and teaches the body to make T cells and antibodies to block and kill COVID.

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

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

Professor Matthew Snape, Lead Investigator and the University of Oxford, said the findings did not undermine the UK policy of giving people the same vaccine shot twice. We already know that both the standard schedules are effective, and against hospitalizations and severe diseases. It includes against the Delta variant when given at eight to 12 weeks apart in the UK.

Is it the autumn booster dose?

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

Experts also say that it is too early to know if people will require a booster dose this year ahead of winter or not. It is unclear yet how much immunity might wane over time.

“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,” says Professor Paul Hunter from the University of East Anglia.

He also suggested that people who have had the first course of AstraZeneca might be offered Pfizer as a booster rather than a repeat of AstraZeneca. It is also true that 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 the mix and match vaccine trial are highly encouraging and throw up some interesting options for booster doses.

Mixing up the second and first doses of Pfizer-BioNTech and Oxford-AstraZeneca vaccines yields strong immune responses. Indeed, each combination of dosing – Pfizer/Pfizer, AZ/Pfizer, or Pfizer/AZ produces higher antibodies and cellular responses compared to AZ/AZ.


You must also not forget that the two doses of AstraZeneca are already proven to reduce the chances of being hospitalized with COVID by more than 90%. So we know from real-world evidence that the AstraZeneca vaccine is quite effective. Currently, the gap between the first and second doses is between 8 to 12 weeks, which must give a better immune response. It may be preferable to give a different brand of vaccine than the one used for the first two shots, but it may also be worth noting that mixing the vaccines does produce more short-term side effects like muscle pain, headaches, and chills.

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