is it “the same” for the booster dose against Covid-19, as Olivier Véran says?

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Which vaccine to choose? The question torments many French people when they make an appointment for their COVID-19 vaccination booster. “It can be Moderna or Pfizer, indiscriminately”, replied the Minister of Health, Friday, December 3 on franceinfo. “I say to French people who have had for example two doses of Pfizer and who are worried about having Moderna: no problem. Likewise, the French who have had Moderna twice and who are will offer Pfizer: no worries, it’s the same “, wanted to reassure Olivier Véran.

“The only difference is that if you are under 30, we prefer to give you Pfizer rather than Moderna”, assures the Minister of Health. Do scientific studies and drug specialists prove him right?

A slight advantage to Moderna over Pfizer after two doses

In the match between these two messenger RNA vaccines, Moderna appears to have a slight advantage over Pfizer. A recent study, conducted by American researchers from Harvard and Boston universities, confirms this trend, already observed by several studies, as reported by the High Authority for Health on November 8. These jobs (in English) were published on December 1 in the New England Journal of Medicine (NEJM). The state of health of more than 400,000 veterans of the United States Army, vaccinated with either Pfizer or Moderna, was monitored between January and September. The two vaccines see their effectiveness level off or even decrease a little over the months.

But more than five months after the injection of the two doses, Moderna’s vaccine appears to be slightly more effective than that of Pfizer, both against the Alpha variant and against the Delta variant, which is more contagious. Cases of infection, symptomatic forms of Covid-19, hospitalizations, admissions to intensive care units and – to a lesser extent – deaths are in slightly lower proportion after two doses of Moderna than after a Pfizer vaccination. The gap is small, however. : 1.2 to 1 000 for contamination, and 0.02 to 1 000 for deaths due to Covid-19.

“We have a little more antibodies with the Moderna than with the Pfizer, which was expected, because the Moderna is a little more dosed than the Pfizer”, tempers Professor Jean-Louis Montastruc, head of the pharmacology department at the Toulouse University Hospital. The two initial doses of Moderna thus contain 100 micrograms of vaccine each, compared to 30 micrograms for the doses of Pfizer. What confirms Mathieu Molimard, head of the medical pharmacology department at the Bordeaux University Hospital.

“We were a little bit more effective with Moderna’s vaccine than with Pfizer’s vaccine because of this initial overdose.”

Mathieu Molimard, pharmacologist

to franceinfo

The composition of the lipid nanoparticles that encapsulate messenger RNA also differs between Moderna and Pfizer. This could also explain this slight increase in efficiency of the first over the second, argue the authors of the study published in the NEJM.

“The downside to this initial overdose is that there is a little more risk of side effects” with Moderna than with Pfizer, explains Mathieu Molimard. During the vaccination campaign, a risk of hospitalization for myocarditis (but also for pericarditis) appeared in particular in the seven days following the injection, in particular with the Moderna vaccine, more often in young men under 30 years and after the second dose. This finding, amounted to 131.6 cases in excess for a million doses of Moderna injected (against 26.7 with the Pfizer), was drawn up by the Epi-Phare survey on November 8. “This risk of vaccine myocarditis is still less frequent and less serious than the risk of myocarditis induced by the virus, emphasizes Mathieu Molimard. In those over 30, there is no significant excess risk. “ Based on these observations, the HAS recommended not to use the Moderna vaccine for those under 30 years of age.

A “booster” effect regardless of the booster vaccine

What about as part of a booster dose? British researchers have studied the ability of different vaccines to trigger an immune response with a dose of “booster”, whether it is Pfizer, Moderna, AstraZeneca, Janssen or CureVac, Novavax and Valneva – some of these products do not. ‘not yet approved in the UK or EU. Their study, conducted on nearly 3,500 people during the month of June, was published in the Lancet (in English) December 2.

In almost all of the settings, the booster doses generated an increased amount of antibodies in the participants. With the exception of the combination of two doses of Pfizer and a booster of Valneva. In France, this scenario is not likely to occur: the Valneva vaccine has no authorization and only messenger RNA vaccines (Pfizer and Moderna) make up the booster doses. However, “this study seems to give the Moderna vaccine a small advantage on the levels of antibodies produced“, notes Dominique Deplanque, president of the French Society of Pharmacology and Therapeutics. “But one cannot conclude definitively on the basis of a single study of this type”, warns the professor of pharmacology.

The study has many limitations. Some third doses were injected very soon after the initial vaccination. In some cases, there was less time between the second and third doses than between the first two. Above all, researchers do not measure the real effectiveness of vaccines against Covid-19, but only the reactions of the immune system, through the level of antibodies produced by the body. However, as Jean-Luc Montastruc reminds us, “Contrary to intuitive logic, there is not necessarily a correlation between the biological level of antibodies produced and the clinical efficacy of a vaccine”.

Regarding the side effects of booster doses of Moderna, “so far we have not had a warning signal”, remarks Mathieu Molimard. This is confirmed by the National Medicines Safety Agency (ANSM) in its latest update on the surveillance of vaccines against Covid-19, posted online on December 3. Including primary vaccinations and booster shots, more than 11.4 million doses of Moderna have been injected as of November 25. Some 15,959 cases of adverse effects were analyzed by the regional pharmacovigilance centers: 82% were non-serious cases and “no new signal “, nor “no new events to watch” was not “identified”. “Given the number of people who have received one or the other of these vaccines in the world, we now know perfectly well the safety profile of vaccines and the side effects that can result from vaccination”, Dominique Deplanque slice.

Pfizer and BioNTech further said in a statement Wednesday, December 8 that, according to their preliminary studies, their vaccine was “always effective” against Covid-19, but also against the Omicron variant, after the injection of “three doses”. The latter variant, considered as “highly transmissible by WHO”, not being “probably not sufficiently neutralized after two doses”.

A “cocktail” of potentially beneficial doses

Receiving a third dose of Moderna after two doses of Pfizer or after a viral vector vaccine, such as AstraZeneca or Janssen does not pose “no problem”, assures Mathieu Molimard. This approach has in particular been validated by experience feedback, argues Dominique Deplanque. In the UK, AstraZeneca’s vaccine was used extensively during the initial vaccination campaign, but messenger RNA vaccines were preferred for the booster campaign. Likewise, in France, caregivers were first vaccinated with a first dose of AstraZeneca, then a second dose of a messenger RNA vaccine, recalls the pharmacologist.

“Boosting with a messenger RNA vaccine after vaccination with a viral vector vaccine increases the antibodies tremendously and provides good immunity.”

Mathieu Molimard, pharmacologist

to franceinfo

“Not only is there no problem, but it is not impossible that making a messenger RNA vaccine after doing a vaccine such as Jannssen or AstraZeneca could further improve the immune response., remarks Dominique Deplanque. The immune response will be based on the ‘foreign substance’ presented to the immune system. If this ‘foreign substance’ is only partially identical to that of the first injection, it expands the repertoire of the immune response. ” The European Medicines Agency (EMA) also issued an opinion on Tuesday, December 7. (in English), validating this so-called “heterologous” vaccination scheme.

“We must reassure everyone, insists Dominique Deplanque. Pfizer and Moderna are based on the same principle (they are both messenger RNA vaccines), their level of efficacy is comparable and the profile of side effects is generally the same, apart from this small increased risk of rare myocarditis and not serious in young adult males. “ And Mathieu Molimard to conclude: “The best vaccine is the first one for which one is eligible and which is available.”

Moderna’s booster dose poses however “logistical problems”, recognizes Dominique Deplanque. “In booster vaccination, we switch to a half-dose of Moderna, explains Mathieu Molimard. There were about ten doses of vaccine in a vial of Moderna. By switching to a half-dose as a booster vaccination, that makes about twenty doses per vial. ” Gold, “twenty doses in a general practice or in a pharmacy, it is not easy to administer, you will spend your day there”. An opinion shared by Jean-Paul Hamon, Honorary President of the Federation of Doctors of France. “It is perhaps easier today to use Moderna in vaccination centers, rather than in pharmacies”, judge Dominique Deplanque.


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