"Second appointment in 6 weeks": this is what vaccination platforms against Covid-19 have been systematically offering since May 10, 2021, the date of the general opening to all adults. However, this delay was only 3 weeks in the spring in nursing homes. And then here is that on the eve of summer, June 15, Olivier Véran announces a flexible dose spacing between 21 days and 49 days. What elements made it possible to change the situation in this way? Would the vaccine also take up its summer quarters?

"The criterion is to have antibodies when you cross the virus"

To understand, you have to go through a few scientific reminders. First of all, this mentioned delay of 21 to 49 days between the two injections only concerns messenger RNA vaccines from Pfizer-BioNTech (Comirnaty) or Moderna (mRNA-1273). Unlike the vaccine developed by AstraZeneca (Vaxzevria) for which you have to wait between 9 and 12 weeks to receive the second injection. Knowing that the question does not arise for the 4th vaccine authorized in France: the Janseen from Johnson & Johnson is administered in a single dose.

"The criterion is to have antibodies when you cross the virus", simply recalls Professor Edouard Tuaillon, virologist at the Montpellier University Hospital. Vaccination allows the body to produce its own antibodies to fight the infection if necessary. For immunity to take hold, two steps are necessary. The primary response linked to the first injection is slow and sets the stage. The second injection is a "boost vaccine". The response is faster and more intense with a greater production of antibodies, able to react over the long term in the presence of the virus.

From the point of view of implementation, it is the High Authority for Health (HAS) and particularly the Vaccine Strategy Guidance Council (COSV), chaired by Alain Fischer, which advises the government on the deployment of vaccination in France. The HAS recommended in February to follow the summary of product characteristics (RCP), provided with the marketing authorization (MA) and which comes from phase 2 and 3 clinical studies carried out during the development of the vaccine. Thus for Pfizer, the spacing of the doses has been tested and positive results are observed following two injections 3 to 6 weeks apart. As well as for each drug, the mode of administration, storage, the necessary doses are taken from the results of clinical studies and are specified in the SPC. The whole is then revalidated by long-term scientific monitoring.

An effective "boost" from the 3rd week

Three weeks is the validated minimum threshold for messenger RNA vaccines; date from which the second injection will be able to cause this expected "boost" effectively. "We are starting to get some perspective on these new messenger RNA vaccines. It works quite well! We already have a lot of data at three weeks with an excellent response", underlines Rodolphe Thiébaud, professor of public health at the University of Bordeaux. . With his teams, he manipulates the figures in all directions to make them speak and simulate the best vaccination schedule to apply depending on the conditions. In the spring, in a context of apprehension of the third wave, the government seized on this low range validated by the manufacturers because "we were in a hurry". It was a question of breaking the chains of contamination in the Ephad. Residents received two doses spaced three weeks apart. “We wanted to limit the spread by first protecting fragile people in a context of limited number of doses”, confirms Samuel Alizon, research director, specialist in the evolution of viruses at Inserm.

A vaccination campaign has two dimensions: protecting each individual and protecting the population. “From the collective point of view, it is better to vaccinate people with two doses than a larger number of individuals with a single dose”, he continues. Individual protection being less after the first injection, this favors the installation of variants. "Today, the public health strategy is to vaccinate as many people as possible with a complete vaccination schedule" (2 doses), confirms Rodolphe Thiébaud. This is all the more significant in this period of propagation of the new delta variant (formerly called Indian variant). “In a vaccinated population, if a variant arises, it will not be able to spread successfully among vaccinated subjects and it will quickly die out.”

This is unfortunately confirmed by the situation in Great Britain currently overwhelmed by the Delta variant, where the strategy has been to vaccinate as many people as possible with a first dose.

Adapting to the life of the epidemic, and that of people

"Science is progressing with the transition to real life. The proposals for adapting calendars are adapted to the life of epidemic and to people's lives", agrees Professor Brigitte Autran, professor of medicine, immunologist and COSV member. The objective today is not to break the rhythm of vaccination during the summer period. The possibility of receiving a second dose after a delay of 21 to 49 days is "a pragmatic announcement from the government which brings flexibility to the organization in the field" supports the HAS. "There is no alteration in the immune response if the time between two doses is extended to 7 weeks", specifies Professor Brigitte Autran. Each new context leads to an adaptation of the strategy: "A fair balance between an immune ideal of the vaccine response and an ideal of vaccine protection in an environment where the virus circulates", confirms Edouard Tuaillon. It is a desire to adapt as well as possible to the life of the vaccine, of the populations, of the virus, always relying on proven scientific data.

Olivier Véran's announcement to extend the possible range between the two injections is based on the evaluation work of the COSV and allows everyone to adapt their schedule. "Go to the end of what we can do in terms of spacing, under validation control, so that everyone can be vaccinated this summer in good conditions", concludes Brigitte Autran.

By Valerie Handweiler