New generation Covid-19 vaccines could soon arrive in France. Called “bivalent”, these messenger RNA vaccines produced by Pfizer and Moderna laboratories target both the historical strain of the virus and its Omicron variant. There are two versions: a vaccine effective against the original virus and the Omicron BA.1 subvariant, another against the original virus and the Omicron BA.4 and BA.5 subvariants. It is particularly this latest version that is of interest, since BA.5 represents more than 95% of samples in France and is the majority in many countries around the world.
In the United States, the Food and Drug Administration (FDA, the American drug agency) has authorized bivalent vaccines Pfizer BA.4/BA.5 and by Moderna. In Europe, the European Medicines Agency (EMA) has authorized bivalent vaccines BA.1 from Pfizer and by Moderna and authorized BA.4/BA.5 from Pfizer monday september 12. In France, the decision to market new vaccines is based on the opinion of the High Authority for Health (HAS), which was expected on September 12. But as autumn approaches and, with it, a potential new wave of Covid-19, new questions arise: are these vaccines really more effective against Omicron? Should we wait until they are on the market to be injected with a 4th dose and, if so, which one to choose, BA.1 or BA.4/BA.5?
“Historic” vaccines remain safe against severe forms
Omicron and its subvariants feature escape capabilities. Historical vaccines are therefore less effective than for previous strains. They do not prevent, or very little, the infection and the transmission of the virus. The protection that the historical vaccines grant against severe forms of Omicron is also less good than for the previous strains, but it remains “very effective”, with “an effectiveness on hospitalizations and on the transition to critical care of 80 and 92 %”, ensures the French Society of Pharmacology and Therapeuticswhich cites numerous scientific studies.
“Scientific data indicate that booster doses provide good protection – through the production of neutralizing antibodies – against severe forms of Omicron and its subvariants, but that this protection decreases after three months in those under 65 years and rather after a month and a half in the oldest and the immunocompromised”, specifies Morgane Bomsel, virologist and CNRS researcher at the Cochin Institute.
Lack of data on the efficacy of bivalent vaccines
As for bivalent vaccines, there are certain certainties, but also questions. The two versions BA.1 and BA.4/BA.5, for example, passed the security tests. In other words, we know they are not toxic to humans. “There was no reason for it to be very different from vaccines based on the historical strain”, comments Morgane Bomsel. We also know that these vaccines, which encode the Spike protein of the BA.1 sub-variant or that of the BA.4/BA/5 sub-variants, are supposed to allow our immune system to produce more effective antibodies against Omicron. At least in theory, because in practice there is a lack of data to confirm that this will indeed be the case. The Pfizer and Moderna laboratories did not have the time to conduct clinical efficacy trials.
“The bivalent BA.1 formulation currently approved is based primarily on laboratory tests using neutralizing antibodies in human serum; and the bivalent BA.4-BA.5 has been approved in the United States on the sole basis of ‘Efficacy trials conducted in rodents, in addition to studies on its safety in humans,’ explains Antoine Flahault, epidemiologist, director of the Institute of Global Health and professor at the Faculty of Medicine of Geneva. “We don’t actually know much, confirms Morgane Bomsel. I have been looking for data on protection for some time and for the moment we only know that the laboratories claim that a booster with a bivalent vaccine leads to the production of antibodies more effective than with a booster of a ‘historic’ vaccine, except that they do not indicate whether it is 10, 20 or 30 times more effective”.
Awaiting “real life” results in the United States
But then, when the choice arises between the bivalent BA.1 vaccine and the BA.4/BA.5, which should be chosen? BA.1 was developed a little earlier, and scientists have more scientific data about it. Nevertheless, the logic would like that BA.4/BA.5 is preferred, since it is this last sub-variant which is very largely majority. “The BA.1 bivalent already seems a little outdated to me today and might not appear much more effective than the original monovalent”, notes Antoine Flahault. As for BA.4/BA.5, the specialist believes that it is appropriate to wait for data from “real-life experience conducted in the United States”, where the bivalent vaccines from Pfizer and Moderna are widely distributed.
In conclusion, according to the expert, people who have not been vaccinated or infected for more than three months should not wait for bivalent vaccines to be injected with a fourth dose. “We know today that people who have received four doses of monovalent vaccine are hospitalized less often than those who have only received three, whereas for the bivalent vaccine, we do not yet have these data. 11. In all cases, the fourth dose is therefore highly recommended and without delay for all adults eligible for vaccination, and in priority for people at risk of serious forms”.
For her part, Morgane Bomsel bases her hopes on mucosal vaccines, which are injected into the nose and make it possible to stimulate immune protection in the upper respiratory tract and therefore block the entry point of the virus. With sufficient protection, these vaccines, coupled with injection vaccines, could block the spread of the virus and potentially end the pandemic. “There are about ten clinical trials in the world on mucosal vaccines. The Chinese vaccine from Sinovac has just been released and researchers have demonstrated that it can block transmission in animal models, indicates the researcher. There are not many scientific publications yet, but it seems quite clear that mucosal vaccines which will give a good immune response at the nasal level will make a real difference in the fight against Covid-19. It is still very recent, but we will start to see the results in a few months.”