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should we fear a major impact of variants on vaccination?

by archyw

Creteil, France –Indian, Brazilian, South African, Californian, English and even Breton or Bordeaux… fears of seeing vaccination become ineffective in the face of the emergence of new variants of SARS-CoV2 have increased. Should we be worried about this evolution of the epidemic? Is there a risk that a variant will escape the immune response? What vaccine strategy is planned to fight against variants?

To shed light on the impact of variants on vaccination, we interviewed the Prof. Jean-Daniel Lelièvre, head of the clinical immunology and infectious disease department at Henri-Mondor hospital (AP-HP, Créteil). The virologist recalls that the variants cannot completely escape the immune response and that the latest data on the effectiveness of vaccines remain reassuring.

This is what theWorld Health Organization (WHO) said last Thursday at an online press conference. “All the variants of the Covid-19 virus that have appeared so far respond to available and approved vaccines,” stressed Hans Kluge, director of WHO Europe. However, he called for vigilance, in particular to prevent the spread of new variants.

Whether with the English, South African, Brazilian, Indian or other variant, their appearance is problematic since the mutations have brought a selective advantage.

Medscape French edition: What is the current situation in France regarding SARS-CoV2 variants and should we be concerned?

Prof. Jean-Daniel Lelièvre: The English variant B.1.1.7 has become the predominant viral strain circulating in our territory. Whether with the English, South African, Brazilian, Indian or other variant, their appearance is problematic since the mutations have brought a selective advantage. This can be linked to the appearance of mutations on the RBD (Receptor-Binding-Domain) domain of the Spike protein of the virus which is used to bind to the ACE2 cell receptors and which is also targeted by the neutralizing antibodies. In the case of the South African variant B.1.351 and the Brazilian variant P1, which have several mutations on the spike protein, this problem appears to be more important. Concerning the Indian variant B.1.617, no sufficient data are yet available. The appearance of this variant is not, however, the major cause of the ongoing disaster in India.

Which variants are the majority in France?

According to the last epidemiological point of Public health France (SPF), dated May 13, 2021, the proportion of suspected English variant 20I / 501Y.V1 (line B.1.1.7) is 79.5%, making this variant the strain of SARS-CoV2 virus mainly in circulation in France . The proportion is 5.6% for the South African 20H / 501Y.V2 or Brazilian 20J / 501Y.V3 variants, “with departmental heterogeneity”, specifies SPF. The Indian variant B.1.617 has been observed for “a fortnight”, but its distribution is not yet considered to be of concern.

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What about the risk of a SARS-CoV2 variant escaping acquired immunity and then having an ineffective vaccine?

Pr Lelièvre: First of all, it should be understood that the immune response to these variants is as good as that directed against the old strain. If an increase in mortality is observed with certain variants [voir notre article Variant britannique du SARS-CoV-2 : 64% plus meurtrier], it is because of their virulence, not necessarily of the immune response.

A variant cannot completely escape the immune response. We are not witnessing new contaminations by the thousands among people infected last year. The cases are marginal. Variants may indeed be less sensitive to a pre-existing or post-vaccination immune response and induce reinfection. There may be a loss of effectiveness of neutralizing antibodies. But, in any case, there will be an absence of reaction. And then, immunity is not limited to the humoral response. There are other types of response, for example through cytotoxic CD8 T lymphocytes.

Regarding the efficacy of vaccines, it seems that it is not much reduced in the face of variants, at least for RNA vaccines and the Janssen vaccine.

Regarding the efficacy of vaccines, it seems that it is not much reduced in the face of variants, at least for RNA vaccines and the Janssen vaccine (Johnson & Johnson). Recent results have shown an efficacy of 64% at 28 days with the Janssen vaccine in South African patients, despite the majority presence of the South African strain [1]. The drop in efficiency is slight. And, the rate of protection against severe forms of Covid-19 remains excellent. Encouraging results have also been reported with the RNA vaccine Pfizer / BioNtech, associated with an efficacy at two weeks of 75% against the South African variant B.1.351 and of 89.5% against the English variant B.1.1.7 [2]. These data obtained after a mass vaccination in Qatar, where these two variants are the majority, also show an effectiveness of more than 97% against severe forms of Covid-19.

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If vaccination is more effective on certain strains, even slightly, isn’t there a risk in the long term of favoring less sensitive strains?

Pr Lelièvre: Let’s be clear: the appearance of variants is part of the natural evolution of an epidemic in a population that is not immune and therefore unvaccinated. When vaccination is sufficiently important, it could possibly lead to the selection of certain variants. But this is only a hypothesis. For the moment, nothing proves it. And, for that, the vaccines would have to become totally ineffective on the variants.

In Denmark, where the sequencing of viral strains of SARS-CoV2 is widely practiced, variants have not become the majority in people with vaccine failure. There is no major modification in the distribution of the variants. This selection of variants by vaccination is a hypothesis which is, for the moment, a fantasy.

What vaccination strategy is envisaged to ensure that the immunity acquired after vaccination remains effective against the variants?

Pr Lelièvre: First of all, it should be kept in mind that the immune response modulates over time after a vaccination or an infection, in particular in reaction to the viral proteins which are preserved in the follicular dendritic cells. In this sense, it is possible that immunity acquired after infection with the original virus provides better protection against variants.

To deal with the variants, a vaccine booster can be used to improve the response against the variants. It has recently been demonstrated that a booster with an RNA vaccine, without modification of its composition, allows the production of antibodies against the variants in people previously infected with the original strain of SARS-CoV2. [3]. The immune response evolves by targeting domains that are found conserved in the mutated spike protein.

All vaccines currently available can be modified to include new variants, but there is no evidence at this time that this is necessary.

Will simple vaccination reminders be sufficient to deal with the emergence of variants or should we move towards the development of new vaccines?

Pr Lelièvre: Vaccination is required to evolve, with a booster at six months or at one year using the same vaccines or vaccines modified to better target the variants. The reflection is underway and the decision will depend on the results obtained in the clinical trials which are currently being carried out to answer these questions. All vaccines currently available can be modified to include new variants, but there is no evidence at this time that this is necessary. Moderna has announced the evaluation of a multivalent vaccine including the mRNA of the spike protein of the original strain and that of the South African variant B.1.351. However, the need for such a vaccine has not been demonstrated. On the contrary, as I said previously, a simple reminder seems sufficient for the moment.

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Do you think it is still possible to achieve collective immunity?

Pr Lelièvre: It is a complex question. It depends on what is meant by collective immunity. If this is considered as a level of immunity allowing those who are not vaccinated / infected to be protected by those who are, the percentage depends in particular on the R0, the basic reproduction number, itself dependent different viral strains. This percentage is then high and involves widely vaccinating children. So there are still a lot of unknowns and it is likely that we will not achieve this collective immunity, at least not in the short term.

Variants of concern, of interest or under surveillance

Among the SARS-CoV2 viruses circulating in Europe, four variants are considered to be of concern for the European Center for Disease Prevention and Control (ECDC) due to greater transmissibility or increased virulence. Two belong to the line of English variants (B.1.1.7), the other two are the South African and Brazilian variants.

The European agency also has nine “variants of interest”, viral strains whose impact on transmissibility, severity of infection or immunity is suspected, but not proven with certainty. There are variants that were detected for the first time in France, Nigeria, the Philippines or Colombia. Also included is the Indian variant, however classified as of concern by the WHO.

Finally 17 variants are “under surveillance”. “There are indications that they may have properties similar to those of the variants of concern, but the evidence is weak or has not yet been evaluated,” says ECDC.

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