Covid-19 vaccine: a 4th dose for what? Who is concerned ?

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 the interest of the fourth dose (second booster), 18 months after the launch of the vaccination against the Covid-19 and following the seventh vague of the’epidemic with the Omicron BA.4 and BA.5 variantsand provides an update on the effectiveness of current vaccines against the variants Omicron.

The Conversation: The vaccines currently in use were designed from the initial strain of SARS-CoV-2 that emerged in Wuhan. At present, what is known about their effectiveness against Omicron variants?

Judith Muller: Immunological research has shown that the 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 following vaccination. An identical phenomenon is observed for antibodies acquired following an infection.

This is a normal natural mechanism: viruses evolve depending on the antibodies they encounter, and more specifically the given antibodies protecting against this infection. The genetic evolution in these virus selects structures less well recognized by antibodies, with the consequence of maintaining the capacity for infection in an immunized population – this is immune escape.

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

The question is therefore rather this: could we, in the future, because of these genetic adaptations, see the emergence of a variant against which vaccination no longer or little protected against severe forms? It would rather be an unfortunate coincidence – it cannot be ruled out, but it is unlikely.

TC: We must therefore not confuse protection against severe forms of Covid-19 with protection against infection…

JM: Indeed, these are two different things and it can be confusing. Protection against infection (often referred to as “symptomatic infection” in studies) declines quite quickly after vaccination against Omicron variants: it is less than 30% (<30% of episodes are avoided) beyond three months.

On the contrary, the protection against hospitalization or death in case of infection moves very little with time and variations. As a result, the overall protection against severe forms (which includes protection against infection) stays good against Omicron variants and has decreased only slightly since vaccination.

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

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

JM: You have to be aware 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 to 70% after the initial regimen (without reminder). In other words, 6 out of 10 cases of Covid-19 with complications can be prevented by vaccination. But the other 4 episodes will occur nonetheless. This can make a lot of people at the same time in hospitals, 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 (from the age of 50) and you are exposed to a high risk of infection (as during an epidemic wave).

It is now considered that the booster is part of the complete vaccination scheme to obtain good protection against severe forms. The same reasoning also applies to unvaccinated people who have been infected – a vaccine dose complements immune protectionmakes it more durable and more solid against variants.

TC: There have been discussions about whether to lower the age for this second recall. Why ?

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

An additional booster also greatly reduces your risk of being infected (and infecting others) for about three months. For elderly or immunocompromised people, this means optimizing their protection. For younger adults living or working near vulnerable people, this helps secure contact for a certain period.

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

TC: Who is concerned today by 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 immunocompromised people. The recommendation now also covers adolescents and adults under 60 with risk factor for a severe form (diabetes, obesity…), including pregnant women from the first trimester of pregnancy.

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

As explained previously, the idea here is to close “the window » of risk by being beyond 80% protection.

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 technology similar to that used to produce most vaccines against flu seasonal. This could eventually convince people who would still be reluctant to use vaccine technology to messenger RNA.

It is currently authorized in adults aged 18 to 50 only, 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. His efficiency should probably be as good than that of the Vaxzevria vaccine (from Astra Zeneca) or mRNA vaccines.

It remains to be assessed at what level this vaccine protects against Omicron variants, since clinical trials have been conducted on the Wuhan strain. And of course, it will be necessary to observe closely the duration protection against infection and severe forms.

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

TC: Speaking of which, there have been no new side effects 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 young people within a week after vaccination has since been observed more accurately – these myo – or pericarditis usually evolve without complications or sequelae. 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 an effect of vaccination, it is of course necessary to compare the frequency of these disturbances in vaccinated women to that ofwomen not (yet) vaccinated, for example in a clinical trial or in an epidemiological study after large-scale use.

According to the EMA, the available data make it possible to rule out a link between vaccination and the absence of periods, but data are still awaited for a possible link with heavier bleeding.

If they are 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 further considered and evaluated in clinical trials.