Since circulating SARS-CoV-2 variants, a crucial question arises: will the vaccines used against the “historic” strains be as effective in protecting us from them?
This question is legitimate: at the end of March, South Africa announced that it had sold all its doses of the AstraZeneca vaccine. Scientific work had indeed revealed that it was less effective against the variant circulating in this part of the world (variant 20H / 501Y.V2 belonging to the line B.1.351).
What about RNA vaccines? Researchers have tried to find out. Published in the journal Cell, their results suggest that certain variants currently in circulation could have the capacity to escape acquired immunity, whether during a first infection with the “historic” strain of SARS-CoV-2 or following vaccination.
While this work indicates that vigilance is required, it is however much too early to draw conclusions as to the possible clinical consequences. Explanations.
What is vaccine escape, and how is it studied?
When the environmental conditions are optimal (adequate temperature, abundant food…), microorganisms such as bacteria or viruses can multiply exponentially: they then produce immense quantities of copies of themselves. In doing so, they make mistakes. Some are neutral, in other words, they are neither beneficial nor harmful to their carriers. Others are harmful, which can lead to their extinction. Finally, some provide an advantage that will allow the microbes that possess them to gain the advantage over their competitors.
These advantages can be of different types: ability to feed on a new resource, acquisition of a new defense mechanism, resistance to new environmental conditions, etc. The resistance to antibiotics developed by certain bacteria results from such “beneficial” mutations. Another example is vaccine escape, which allows infectious microorganisms to escape the immune response designed to kill them.
Read also : How do germs escape vaccines?
To study the infectivity of viruses without having to handle dangerous viruses, virologists have developed “pseudotyped retroviral particles”. These tools are in a way “pseudo-viruses”: they are particles containing only the genes involved in the manufacture of the viral envelope of the virus to be studied. It is on the latter that are found the “keys” that allow the virus to enter the cells that it infects (in the case of the SARS-CoV-2 coronavirus, this key is the Spike protein, or S).
To these genes, researchers add a gene that produces a fluorescent protein. Thus, if the pseudo-viruses manage to penetrate into the target cells, the latter become fluorescent, which facilitates their detection.
This tool made it possible to understand, for example, certain mechanisms of entry of hepatitis C virus into liver cells. It is also commonly used for highlightthe blockingviral entry by antibodies from patients. If they are “neutralizing”, the antibodies in fact prevent interactions between the proteins used by the virus to penetrate into the cells and the corresponding receptors, in other words the “locks” located on their surface. In such a situation, the virus remains at the door …
American, German and South African researchers have used this approach to study the ability of sera from vaccinated individuals to neutralize the SARS-CoV-2 Spike protein. What does this work reveal?
Mutations that promote immune escape
The authors were interested in the two available messenger RNA vaccines, namely that of Pfizer / BioNtech (trade name Cominarty®, mainly used in France where it represents 65.4% of the first doses administered) and that of Moderna (minority with 7.7% of the first doses). They collected the sera of 99 vaccinated patients after one, then two injections of vaccines, then tested the capacities of these samples to neutralize the original S protein, the one carrying the D614G mutation and the S proteins of the so-called “British” variants. “(Line B.1.1.7),” South African “(line B1.1.351) and” Brazilian “(line P1).
The results show that the two messenger RNA vaccines effectively protect against the original virus, against the D614G variant and against the British variant, especially after two vaccine injections. On the other hand, the antibodies of the patients little neutralize the protein S of the South African and Brazilian variants, which suggests that these vaccines could have low efficacy against these variants. This work seems to indicate that a small number of mutations could be sufficient for SARS-CoV-2 to escape the immune response induced by these vaccines.
However, the consequences of this finding for the population remain to be established, as the authors themselves point out.
To remain vigilant
This very rigorously conducted study remains an “in vitro” study; it does not allow conclusions to be drawn as to the clinical consequences of these results obtained on cells in culture. In particular, information is missing on cellular immunity vaccinated people, which could protect them despite the absence of “humoral” immune protection, ie by antibodies.
In addition, it could also have been interesting to study on the same principle the neutralizing capacities of sera from people vaccinated with the AstraZeneca vaccine or that of Johnson & Johnson, a single-dose vaccine available in pharmacies since April 24. To know the capacities of pseudotyped retroviral particles based on the so-called “Indian” variant (20A / 484Q, line B.1.617) to escape the effects of vaccines could also prove useful: this would provide clues about their potential role, still discussed, in the epidemic currently blazing in India.
Finally, it will be necessary to confirm these results by observations in the population to answer two questions: do the vaccinated people become infected with these variants? If infected, do they develop severe forms of the infection, and in what proportion compared to unvaccinated people?
This news is nevertheless reassuring, in particular with regard to the French situation: the messenger RNA vaccines currently available protect against the British variant which is currently circulating massively in our country.
However, this work underlines the importance of taking the necessary precautions to monitor, and if possible control, the spread of South African and Brazilian variants, in the event that messenger RNA vaccines prove to be less effective against them also in vivo. The measures to control people arriving from regions where these variants circulate are, unfortunately, justified to avoid having to face a new pandemic wave.