Mixing AstraZeneca, Moderna jabs leads to higher antibodies, T-cells

Mixing AstraZeneca, Moderna jabs leads to higher antibodies, T-cells

A study has found that combining a first dose of the AstraZeneca Covid 19 vaccine with a second dose of either the Novavax or the Moderna jabs results in far higher levels of neutralizing antibodies and T-cells than two doses of the AstraZeneca jab.

The finding has important implications for countries that have not completed their primary vaccine campaigns, as it suggests that you don't need access to mRNA vaccines and 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 and 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 determine whether mixing and matching Covid 19 vaccines during primary immunisation schedules could be beneficial to the overall immune response to vaccination. Such flexibility could be crucial to the rapid deployment of vaccines in low and middle-income countries, where vaccine supply may be inconsistent.

Professor Matthew Snape, a professor at the University of Oxford, said that there was a great amount of flexibility in the primary immunisation schedule. Just because you received dose one of a vaccine, doesn't mean you have to receive the same vaccine for dose two. The study shows that using the Moderna vaccine as a booster dose in people who have previously received the AstraZeneca jab will result in high levels of neutralizing antibodies and T-cells.

It follows separate data published last week that showed that both the Pfizer and Moderna jabs can strengthen the body's immune defences.

The 1,070 British participants received a first dose of the AstraZeneca or Pfizer vaccine, followed by a second dose of the same vaccine, or either the Moderna or Novavax jab nine weeks later.

Among those who received the Moderna vaccine followed by AstraZeneca vaccine, levels of neutralizing antibodies were 17 times higher and four times higher among those who received AstraZeneca 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 vaccine resulted in 1.3 times as many neutralizing antibodies than two doses of Pfizer, while receiving Novavax as the second jab resulted in 20% fewer antibodies.

The study, which was 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 small pieces of genetic code known as messenger RNA to human cells, instructing them to manufacture the coronaviruses spike protein themselves, while using a harmless virus to deliver these instructions, 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.

A second dose of Moderna resulted in 1.5 times more T-cells for the Pfizer jab, while a second jab of Novavax resulted in fewer T-cells.

Snape said that the RNA and the viral vector vaccines are doing something quite different when it comes to priming for the T-cell response.

Previous research on other vaccines, such as the Ebola vaccine, had suggested that a mix- and- match approach could lead to enhanced immune responses.

What was 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. When it came to the T-cell response, RNA followed by a protein Novavax was slightly underwhelming. 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 neutralizing antibodies, but there was very little drop-off in T-cell responses.

The World Health Organization and the Medicines and Healthcare Products Regulatory Agency are considering whether to authorise the Novavax vaccine, and are expected to announce their decision within a few days or weeks. The WHO authorisation would allow the vaccine to be delivered via the Covax initiative.

Richard Hatchett, chief executive of the Coalition for Epidemic Preparedness Innovations, said: This is an extremely encouraging and valuable data on the potential to mix and match Covid 19 vaccines in primary immunisation schedules. A second dose of a different Covid 19 vaccine can generate a robust immune response is advantageous in helping the roll out of Covid 19 vaccines through Covax, especially in populations still waiting for their primary immunisation or in those partially vaccinated.