Finding is good news for lower-income countries that have not yet completed their primary vaccination campaigns
Combining a first dose of the AstraZeneca Covid-19 vaccine with a second dose of either the Moderna or the Novavax jabs results in far higher levels of neutralising antibodies and T-cells compared with two doses of the AstraZeneca jab, a study has found.
The finding has important implications for lower-income countries that have not yet completed their primary vaccination campaigns, as it suggests you do not need access to mRNA vaccines – and therefore ultra-cold storage facilities – to trigger an extremely potent Covid-19 vaccine response.
The strongest T-cell response of all was generated by a dose of the AstraZeneca vaccine followed by a dose of the Novavax vaccine – both of which can be stored in a standard refrigerator.
The University of Oxford-led Com-Cov study set out to establish whether mixing and matching Covid-19 vaccines during primary immunisation schedules could be detrimental or beneficial to the overall immune response to vaccination. Such flexibility could be crucial to ensuring the rapid deployment of these vaccines in low- and middle-income countries, where vaccine supply may be inconsistent.
“What we’re seeing is that there’s a great amount of flexibility in the primary immunisation schedule,” said Prof Matthew Snape at the University of Oxford, who led the research. “Just because you’ve received dose one of a particular vaccine, doesn’t mean you have to receive the same vaccine for dose two.”
The study also bolsters confidence that using the Moderna vaccine as a booster dose in people who have previously received the AstraZeneca jab should result in high levels of neutralising antibodies and T-cells.
It follows separate data published last week suggesting that both the Pfizer and Moderna jabs can dramatically strengthen the body’s immune defences.
The 1,070 British participants received a first dose of the AstraZeneca or Pfizer vaccine, followed nine weeks later by a second dose of the same vaccine, or either the Moderna or Novavax jab.
Levels of neutralising antibodies were 17 times higher among those who received the AstraZeneca vaccine followed by the Moderna vaccine and four times higher among those who received AstraZenaca followed by Novavax, compared with those who received two doses of the AstraZeneca vaccine.
For those who started with the Pfizer jab, receiving a second dose of the Moderna vaccines jab resulted in 1.3 times as many neutralising antibodies than with two doses of Pfizer; while receiving Novavax as the second jab resulted in 20% fewer antibodies.
The study, published in the Lancet, also revealed differences in T-cell responses after combinations of different types of vaccines.
Vaccines that are mRNA-based, such as the Pfizer and Moderna jab, deliver a small piece of genetic code known as messenger RNA to human cells, instructing them to manufacture the coronavirus spike protein themselves; viral vector vaccines such as the AstraZeneca jab do the same thing, but use a harmless virus to deliver these instructions; whereas protein-based vaccines, such as the Novavax jab, deliver pre-made fragments of the spike protein alongside an immune-stimulating adjuvant.
While two doses of either the AstraZeneca or Pfizer vaccine resulted in similar numbers of T-cells, combining the AstraZeneca vaccine with a second dose of Moderna resulted in 3.5 times more T-cells. A second dose of Novavax resulted in 4.8 times more T-cells.
For the Pfizer jab, a second dose of Moderna resulted in 1.5 times more T-cells, while a second jab of Novavax resulted in fewer T-cells.
“It tells us that the RNA and the viral vector vaccines are doing something quite different when it comes to priming for the T-cell response,” said Snape.
Previous research on other viral vector vaccines, such as the Ebola vaccine, had suggested that a mix-and-match approach could lead to enhanced immune responses.
“What was a bit more surprising is that we didn’t see that so well with the RNA vaccines – especially when it comes to the T-cell response, said Snape. “RNA followed by a protein (Novavax) was slightly underwhelming when it came to the T-cell response.”
The study also examined the impact of these different vaccine combinations against the Delta and Beta variants. In all cases, there was a reduction in levels of neutralising antibodies, but there was very little drop-off in T-cell responses.
Both the UK’s Medicines and Healthcare products Regulatory Agency and the World Health Organization are currently considering whether to authorise the Novavax vaccine, and are expected to announce their decision within days or weeks. WHO authorisation would enable the vaccine to be delivered via the Covax initiative.
Dr Richard Hatchett, chief executive of the Coalition for Epidemic Preparedness Innovations, said: “This is extremely encouraging and valuable data on the potential to mix-and-match Covid-19 vaccines in primary immunisation schedules. Knowing that a second dose of a different Covid-19 vaccine can generate a robust immune response is advantageous in helping the rollout of Covid-19 vaccines through Covax, especially in populations still urgently waiting for their primary immunisation or in those partially vaccinated.”