Covid vaccine: New study finds switching up second dose generates ‘better immune response’

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The world is on high alert after the emergence of the Omicron variant. The new variant – first detected in South Africa – has sparked fears that it could evade some of the immunity induced by the vaccines. In response, the UK has widely expanded its booster programme with the aim of bolstering people’s immune defences against the incoming threat. A new study suggests opting for a different COVID-19 vaccine after your first dose actually enhances the immune response.

The study, published in the Lancet, found a first dose of Oxford-AstraZeneca or Pfizer-BioNTech followed nine weeks later by second dose of Novavax or Moderna COVID-19 vaccines generated a robust immune response.

What’s more, the AstraZeneca vaccine followed by Moderna/Novavax induced higher antibodies and T-cell responses than getting a two-dose shot of AstraZeneca.

Alongside antibodies, T cells are an essential part of the immune system that targets foreign particles, such as viruses.


Also, a Pfizer-BioNTech/Moderna combination induced higher antibody and T-cell responses than two doses of the Pfizer jab.

Furthermore, Pfizer-BioNTech/Novavax induced higher antibodies than two-dose Oxford-AstraZeneca and this schedule induced lower antibody and T-cell responses than two-doses of the Pfizer jab.

The findings indicate that following up first doses of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines with second doses of the Moderna or Novavax jabs will generate robust immune responses against COVID-19, the researchers noted.

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No safety concerns were raised in this study of 1,070 participants, who took part in the study across nine National Institute for Health Research-supported sites.

This study therefore supports flexible use of these vaccines in primary immunisation schedules, which is crucial to help rapid deployment of these vaccines, especially in low- and middle-income countries where vaccine supply may be inconsistent.

Professor Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial, said: “Thanks to studies such as these, we are now getting a more complete picture of how different COVID-19 vaccines can be used together in the same vaccine schedule.

“Encouragingly, all these schedules generated antibody concentrations above that of the licensed and effective two dose Oxford-AstraZeneca schedule. When it comes to cellular immunity, having a first dose of the Oxford-AstraZeneca vaccine followed by any of the other study vaccines generates a particularly robust response.

“It’s only through the inspiring efforts of the Com-COV2 participants and study teams that we can generate these data; this will help get the world immunised against COVID-19 as quickly as possible.”

In addition, a significantly higher number of short-lived vaccine reactions were reported in volunteers who received a second dose of Moderna compared to those who received two doses of either Oxford-AstraZeneca or Pfizer-BioNTech.

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The study was designed as a so-called “non-inferiority” study – the intent is to demonstrate that mixing is not substantially worse than the standard schedules – and compares the immune system responses to the gold-standard responses reported in previous clinical trials of each vaccine.

Professor Andrew Ustianowski, National Clinical Lead for the UK NIHR COVID Vaccine Research Programme, said: “We really cannot thank the volunteers and staff involved in studies such as Com-COV2 enough. The continued effort from everyone within the study helps to gather more important information on the immune response of vaccine dose combinations.

“This is another set of positive findings discovered by the UK research community, supported by the NIHR, which could be applied globally. Results such as these will help to shape guidance nationally and internationally, allowing populations to be better protected from COVID-19.”

CEO of CEPI Dr Richard Hatchett said: “We’re pleased to have co-funded this crucial area of research, in collaboration with our partners at the University of Oxford and in the UK Government, supporting excellent science conducted in the UK that advances vaccine research for the benefit of all. This is yet another example of the impact that funding innovative R&D can have on our hopes of ending the COVID-19 pandemic.

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