A fourth dose of the Covid-19 vaccine for what? And for whom?

Judith Mueller is an epidemiologist, professor at the School of Advanced Studies in Public Health (EHESP) and researcher at the Institut Pasteur. She returns to interest from the fourth dose (second booster), 18 months after the launch of the vaccination against COVID-19 and following the seventh wave and swell
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The conversation: The vaccines currently in use were designed from the initial strain of SARS-CoV-2 that emerged in Wuhan. What is currently known about its efficacy against Omicron variants?

Judith Mueller: Immunological research has shown that Omicron variants, and in particular BA.4 and BA.5, escape more to neutralizing antibodies and even, a little, to T cell-linked immunity, developed after vaccination. An identical phenomenon is observed for antibodies acquired after infection.

This is a normal natural mechanism: viruses evolve depending on the antibodies they find, and more specifically on the given antibodies that protect against this infection. evolution genetic in these virus it selects structures less recognized by the antibodies, with the consequence of maintaining the infectivity in an immunized population: this is immune escape.

On the other hand, it is not “useful” for a virus like SARS-CoV-2 be more dangerous. This is consistent with the observation that, so far, successive variants have not significantly decreased protection against the risk seriously of Covid-19 provided by vaccination.

The question is therefore rather this: could we, in the future, due to these genetic adaptations, see the appearance of a variant against which vaccination no longer protects or protects little against severe forms? I’d rather it be an unfortunate coincidence, it can’t be ruled out, but it’s unlikely.

TC: So we should not confuse protection against severe forms of Covid-19 with protection against infection…

JM: In fact, these are two different things and it can be confusing. Protection against infection (often called “symptomatic infection” in studies) declines fairly rapidly after vaccination against Omicron variants: is less than 30% (<30% of episodes prevented) beyond three months.

On the contrary, the protection against hospitalization or death in case of infection it moves very little with time and variations. As a result, general protection against severe forms (including protection against infection) holds up well against Omicron variants and has decreased only slightly since vaccination.

The only exceptions are the elderly and those affected by a weakened immune system: their vaccination protection decreases more quickly. because they develop fewer antibodies after their vaccination. These are not so rare cases in our society: genetic disposition, chronic illness or current cancer treatment lead to such immune deficiency.

TC: Why do we talk about the importance of booster doses?

JM: It must be taken into account that this overall protection against severe forms -which I describe as good against Omicron and over time- is far from perfect, since it is around 60-70% after the initial regimen (without reminder). In other words, 6 out of 10 cases of Covid-19 with complications can be prevented with vaccination. But the other 4 episodes will happen anyway. This can cause many people to be in hospitals at the same time, as soon as there is a new increase in infections.

After a booster dose, this protection increases to approximately 80%. This additional protection is all the more interesting the older you are (over 50 years of age) and exposed to a high risk of infection (such as during an epidemic wave).

The booster is now considered to be part of the complete vaccination schedule to obtain good protection against severe forms. The same reasoning also applies to unvaccinated people who have been infected – a the vaccine dose complements immune protectionmakes it more durable and more Crystals and amorphous solids
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TC: There have been discussions about lowering the age for this second recall. Why ?

JM: A second booster dose helps to further increase protection against a severe form. This is especially interesting for older people, in whom the risk of complications is higher. There is no precise threshold, so the recommendation of the fourth dose is currently inconsistent between countries.

An additional booster also greatly reduces the risk of becoming infected (and infecting others) for about three months. For the elderly or immunocompromised, this means optimizing your protection. For younger adults who live or work near vulnerable people, this helps ensure contact for a set period.

A broader fourth dose campaign would be – this is my personal opinion – reserved for an exceptional situation: an epidemic wave with a more dangerous variant, before which transmission must be absolutely and quickly reduced to avoid the worst.

TC: Who cares today about this fourth dose or second booster?

JM: According to the new opinion of the HAS, it is recommended from the age of 60 and for immunosuppressed people. The recommendation now also covers adolescents and adults under the age of 60 with risk factor for a severe form (diabetes, obesity…), including pregnant women from the first trimester of the pregnancy.

The fourth dose is also recommended for people around vulnerable people.

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TC: In this context, at the end of June the European Medicines Agency (EMA) authorized an additional vaccine, that of the French laboratory Valneva. What is the benefit of this additional vaccine, which brings the number of vaccines available in France to six?

JM: This vaccine is based on a technology similar to that used to produce most vaccines against the Influenza agent.
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It is currently authorized only in adults aged 18 to 50 years, as it has not yet been evaluated in older people. Given its technology and the data presented by the EMA, this vaccine should provide substantial protection. Their efficiency should probably be as good than that of the Vaxzevria vaccine (from AstraZeneca) or the mRNA vaccines.

The extent to which this vaccine protects against Omicron variants remains to be assessed, as the clinic tests were performed on the Wuhan strain. And of course, we will have to closely observe the duration protection against infections and severe forms.

The pharmacovigilance data will also be carefully examined, because this is a recent vaccine for which we do not yet have large-scale information, unlike previous vaccines (mRNA, viral vector) that have been administered to millions of people for 18 months .

TC: Speaking of which, haven’t any new side effects been identified with RNA vaccines?

JM: No, nothing essentially new since last summer. This is not surprising, because the number of doses administered and the observation period were already very high last year at the same time.

the risk of myocarditis in youngsters within a week after vaccination has since been observed more precisely – these myo – o pericarditis usually progresses without complications aftermath. Above all, we now know that it is Covid-19 that increases the risk of myocarditis and pericarditis.

There are still some questions about menstrual disorders reported by a good number of women after vaccination. To conclude on the effect of vaccination, it is of course necessary to compare the frequency of these disturbances in women vaccinated atwomen who have not (yet) been vaccinated, for example in a clinical trial or in an epidemiological study after large-scale use.

According to the EMA, the available data allows us to rule out a relationship between vaccination and the absence of the rule, but data on a possible link with heavier bleeding are still awaited.

If transient, menstrual irregularities impact quality of life but do not represent a health or health problem. Fertility. However, I find it interesting that with the vaccination against Covid-19, this quality of life is receiving the attention of the health authorities. It may be considered and further evaluated in clinical trials.