Mix and match regimen of AZ and Pfizer COVID jabs works well

Giving one dose each of AstraZeneca and Pfizer COVID-19 vaccines provides good protection against the SARS-CoV-2 virus, but may be associated with more adverse reactions, according to new clinical trial data.

The Com-COV trial compared two shots with Pfizer/BioNTech’s Comirnaty, two doses of AstraZeneca’s Vaxzevria, and a mixed regimen of one of each jab, and found that all were effective at stimulating a “robust” immune response against the coronavirus, according to the investigators.

The order of the mixed shots seemed to affect the efficacy, however, with AZ followed by Pfizer/BioNTech working better than the reverse – at least when the doses are given four weeks apart.

Data on doses given 12 weeks apart will be reported in the coming weeks, according to the team, led by scientists at the University of Oxford, who also report that the mixed regimens generated a stronger immune response than two doses of Vaxzevria.

“This means all possible vaccination schedules involving the Oxford-AstraZeneca and Pfizer-BioNTech vaccines could potentially be used against COVID-19,” according to the researchers, led by Matthew Snape of the Oxford Vaccine Group.

The highest antibody response was observed after two doses of Comirnaty, while giving Vaxzevria followed by Comirnaty generated the highest T-cell response against SARS-CoV-2. The results are available as a preprint and will eventually be published in The Lancet journal.

An earlier report from the trial focusing on side effects found that feverishness, and other flu-like symptoms were reported more frequently with the mixed regimens, although remained generally mild or moderate in intensity.

The results could help vaccination programmes by allowing different vaccines to be used, particularly in countries where supplies are still limited or socks are nearing the end of their shelf life, and could help inform the best strategy for third-dose booster campaigns.

The data suggests for example that giving Pfizer/BioNTech as a booster to might be preferable to a third AZ dose in people who have had two doses of Vaxzevria, although that requires further study.

Professor Jonathan Van-Tam, deputy chief medical officer for England, said that with current supplies there is no reason to change the current UK policy of same-shot regimens.

The team is also running a second trial – Com-COV2 – which is also looking at mixed regimens involving vaccines manufactured by Moderna  and Novavax.

Third AZ dose generates strong variant response

Meanwhile, a sub-analysis of data from the Oxford-led COV001 and COV002 trials has shown that giving a third dose of Vaxzevria at least six months after the first two raises antibodies in the blood back up to the levels seen after the second dose.

There was a six-fold boost in antibody levels as well as a sustained T-cell response after the third dose, accompanied by higher neutralising activity against the alpha (UK), beta (South Africa) and delta (India) variants of SARS-CoV-2.

Despite the positive results, lead author of the study – Teresa Lambe of the Jenner Institute – said that it is not yet clear whether booster shots will be needed given that the current crop of vaccines seem to have a dramatic impact on hospitalisations and deaths from COVID-19.

The data also fund that a prolonged interval of up to 45 weeks between the first and second dose seems to boost immune responses, and that a single shot induced immunity for at least one year.

“This should come as reassuring news to countries with lower supplies of the vaccine, who may be concerned about delays in providing second doses to their populations,” said Professor Sir Andrew Pollard, chief investigator and director of the Oxford Vaccine Group.

“There is an excellent response to a second dose, even after a 10 month delay from the first.”

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