Is it really a good idea to mix the doses of vaccines?

This Friday morning, the Authorized Health Officer ruled on the thorny case of the second dose for people under 55 who had been vaccinated for the first time with AstraZeneca. The Swedish-British vaccine is now prohibited in this category of the population, due to a risk of severe thrombosis linked to the injection. However, before this ban, 533,000 people under the age of 55 in France had been vaccinated with this product against the coronavirus. The question then arose: what to do in their case?

After weeks of suspense, the Authorized Health Officer has decided: these people will receive a second dose of messenger RNA vaccine, such as Pfizer / BioNtech or Moderna. A decision which – once again – raises questions. 20 minutes make the point.

Is mixing vaccines normal?

“The mixture of vaccines is already practiced in some cases”, notes the researcher in immuno-oncology Eric Billy. For example, for hepatitis B vaccination, different vaccines can be used in the first and second doses because the sera use the same antigen. This is partly what matters in determining whether different doses can be combined: the composition of the vaccines and the antigen used. If they are similar (and there are randomized controlled trials to verify the association), we can theoretically vaccinate with different sera.

Does it work for anti-Covid-19 vaccines?

In the case of Covid-19, messenger RNA vaccines, whether Pfizer / BioNtech or Moderna, and AstraZeneca, have the same antigen, the Spike protein. “But in detail, the sequence is not exactly the same, informs Eric Billy. AstraZeneca uses the original sequence of the coronavirus. Whereas Moderna and Pfizer / BioNtech made some mutations to stiffen the three-dimensional structure of the Spike protein, in order to put it in an active conformation. “A detail that should not prevent making the booster dose effective, according to the researcher.

The Authorized Health Officer mentions in his grade “There are many arguments in favor of this strategy, which has already been put to good use in the context of the development of certain vaccines (HIV in particular), and which has proved to be more effective than the homologous prime-boost approach (ie – say the double dose of the same vaccine) “as well as” numerous studies underway within the framework of the European Vaccelerate program and the first data relating to the use of heterologous prime-boost (with different vaccines) in anti-vaccination. -SARS-CoV-2 still limited but encouraging ”.

The British, in order to vaccinate as many people as possible the first time, have already made the decision to sometimes mix the vaccines for the second dose. However, it is still too early to measure any effects, especially since due to the high viral circulation in the United Kingdom, the results could be biased. An English study had, for example, shown that 56.4% of the population over 80 already had antibodies against the coronavirus. In this case, the first dose of vaccine already works as a booster dose, and the second dose does not have much of an effect or benefit.

But once again, Eric Billy is confident: “In view of the same antigen used, the vaccination should be effective by combining the first dose of AstraZeneca and a second dose of messenger RNA vaccine. “

What interval used between doses?

Whether vaccination should therefore work, remains an open question. What interval should be established between the two injections of doses? This is because the interval between first and second doses for AstraZeneca and for messenger RNA vaccines is not the same. For AstraZeneca, it is recommended between nine and twelve weeks between the two injections, while for Pfizer / BioNtech and Moderna, the time between the two doses is between three and four weeks.

For the moment, people under 55 in France vaccinated with AstraZeneca will be vaccinated twelve weeks after the first injection, said the Haute Autorité de Santé. But that could change according to possible studies. “It would be good to quickly study the first people vaccinated at week 12 with two different doses and see the antibody response,” argues Eric Billy. We could then, depending on the results, test other types of interval. Because obviously, the 533,000 French people concerned have not all received the first dose at the same time, and therefore should not all be administered the second on the same date. “Until then, we can therefore make some observations and modifications according to what we notice,” says the researcher, in order to optimize the interval and the immune response. All the same, more than half a million people are affected.