Vaccines adapted to Omicron: “A 4th dose is highly recommended in all cases”

With the arrival of autumn, the likelihood of a new wave of Covid-19 increases, as does interest in a fourth dose. At the same time, France may allow a new generation of vaccines against Covid-19. On Monday, September 12, the Higher Health Authority will indeed publish an opinion on the so-called “bivalent” messenger RNA vaccines. These new vaccines, made by Moderna and Pfizer, target both the “historic” strain of the virus and its Omicron variant. There are two versions: the first activates protection against the original virus and its sub-variant Omicron BA.1, the second one activates protection against the original virus and its sub-variants Omicron BA.4 and BA.5. As Public Health France reminds us in its epidemiological bulletin of 8 September, subvariant BA.5 represents 95% of cases in France.

Meanwhile, “historic” vaccines, if they do not prevent or only slightly prevent the transmission of Omicron, remain very effective against serious forms, recalls the French Society of Pharmacology and Therapeutics, which cites numerous scientific studies. However, this protection decreases over time, especially three months after the last injection. Several questions inevitably arise: Do bivalent vaccines provide greater or longer protection? Which version is better? Should we wait for their marketing before giving the fourth dose or not? Answer by Antoine Flahaud, epidemiologist, director of the Institute for Global Health and professor at the Faculty of Medicine in Geneva.

L’Express: What to say to at-risk and non-at-risk people who are wondering if they need to wait for bivalent vaccines to get their fourth dose injection?

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The concept of “being in danger” is not as simple as it might seem. If you mean “at risk of severe illness, hospitalizations and death”, then today it is quite clear that we are talking about people who are immunodeficient as a result of the disease or their treatment, or even immunocompromised by old age, or those who are not received at least three doses despite the presence of concomitant diseases (obesity, arterial hypertension, diabetes mellitus, etc.). If we think about the risk of long-term, sometimes very disabling Covid, which seems to be as high as 10 to 20% of infected people, whether they have had a severe form or not, it seems that we are all “at risk” of long-term Covid . .

Therefore, in all cases, the fourth dose, i.e. the second booster dose, is strongly recommended and urgent for all eligible adults, and especially for people at risk of severe forms. We don’t have to wait for a bivalent vaccine, because we now know that people who receive four doses of a monovalent vaccine are less likely to be hospitalized than those who receive only three. For a bivalent vaccine, we do not yet have these data.

Is there, however, information to evaluate the effectiveness of new bivalent vaccines? Or who will determine the differences between BA.1 vaccines and compared to “historical” vaccines, and the benefits of BA.4/BA.5 vaccines?

Today we do not have answers to these important questions. Vaccine manufacturers are chasing new variants and sub-variants. As soon as they produced their first bivalent vaccine with Omicron’s BA.1 sub-variant, BA.2 sub-variants, followed by BA.4 and BA.5, emerged and quickly dominated the global landscape of this pandemic. They then released another bivalent formula for their vaccines containing the BA.4 and BA.5 strains.

But because of the tight release schedule for these new drugs, they didn’t have enough time until the fall to conduct clinical trials of efficacy. Thus, the currently approved bivalent formulation BA.1 is mainly based on tests performed in the laboratory (based on neutralizing antibodies on human serum), while the bivalent formulation BA.4-BA.5 was approved by the FDA. products and medicines. [FDA, l’agence américaine du médicament, NDLR] in the US based solely on efficacy trials conducted in rodents, in addition to studies of its safety in humans. Similarly, the FDA allows changes to the composition of the seasonal flu vaccine. But Covid is not the flu, and we don’t have enough hindsight yet to know if this strategy will prove to be the final one.

Given a choice, which vaccine would be preferred, BA.1 or BA.4/BA.5?

Unfortunately, this question cannot yet be answered. Some experts believe, based on preclinical results, that bivalent vaccines will be more effective against transmission of Omicron than conventional monovalent vaccines that were directed only against the original Wuhan strain. They could then limit the size of the new waves. Others believe that these bivalent vaccines are likely to be a shot in the dark, calling the Omicron sub-options and BA.5 in particular “invisible options”, i.e. passing under the radar of our immunity, leaving no immune memory, whether after infection or a fortiori after vaccination.

For my part, I think we should wait for the first results of the North American experiment in real life, as the FDA has decided to approve the BA.4/BA.5 bivalent vaccine and distribute it widely. Bivalent BA.1 seems a little dated to me today and may not seem much more effective than the original monovalent. The health authorities have actually bet on the effectiveness of these new formulations, which can be evaluated in the coming months.

How likely are new, completely different options this fall/winter?

Today, no one is able to quantify the likelihood of future scenarios of this pandemic. Even in the medium term for next autumn and winter. Is the jump in pollution seen in recent days a harbinger of a new wave at the beginning of the season, when the summer wave has barely ended? Is BA.5 capable of generating a new wave, like last year’s Delta variant, which caused an autumn wave shortly after the summer wave in Western Europe? Will Omicron’s new sub-variant manage to qualify and become dominant in turn? Will it replace BA.5, as BA.5 replaced BA.2, which itself replaced BA.1, or are there several sub-options coexisting this winter?

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You see several possible scenarios here, not to mention more optimistic options such as a longer lull this fall or even a somewhat high plateau but no wave or hospital surge. But I can’t tell you today which is the most likely!


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