In the public health challenge of the fight against the Covid-19 pandemic, the best protection is undoubtedly vaccination. “The risk-benefit ratio, for the population, is in its favor”, guarantees Jean-Daniel Lelièvre, head of the infectious diseases department at Henri-Mondor hospital in Créteil. The studies, now numerous, are formal: the vaccine protects very strongly against serious forms of the disease, unlike a so-called “natural” infection, subject to such complications. But is the immunity developed in the two cases similar? Is one better than the other?
Natural immunity ‘is always better’
“It’s a complex response, which depends on the host – whether it has an immune deficiency or not – and infections. There are people who have severe forms of the disease, others less severe, symptomatic forms, others asymptomatic. The immune response will vary depending on the severity of the initial disease”, explains to L’Express the immunologist, member of the High Authority for Health (HAS). But with regard to clinical data, the effectiveness of the immune response appears better “if one has been infected then vaccinated; then if one has been infected; then if one is vaccinated. Vaccination protects less against an infection than infection versus reinfection,” he points out.
In addition to the variability of the immune response depending on the individual, there is the issue of variants. “If you were infected at the very beginning of the disease, with the historical strain, you will probably have less effectiveness against reinfection with the different variants than if you received three doses of vaccine”, explains Jean-Daniel Lelièvre. Eric Caumes, infectious disease specialist at the Hôtel-Dieu Hospital in Paris, believes that a “variant can more easily circumvent vaccine immunity than natural immunity”. Of the two, the latter is “always better. This is the case for measles, yellow fever… There are almost no exceptions in vaccinology, except perhaps papillomavirus vaccination (responsible for infections sexually transmitted, Editor’s note)”, he assures.
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Wider and longer cellular response
Regarding the current pandemic, the infectiologist refers to a study by the Centers for Disease Control and Prevention (CDC) American published mid-January. Health authorities studied the cases of Covid-19 in the states of New York and California, from the end of May to November 2021. At that time, the Delta variant was in the majority, Omicron did not exist, and booster doses n were not yet so widespread. The study showed that vaccinated and never-infected individuals had a lower risk of contracting the Delta variant than unvaccinated and never-infected people. The risk was even lower for those, unvaccinated, who had already been infected. The CDC notes that work on the Delta variant in other countries “has also demonstrated increased protection of previously infected, vaccinated, and unvaccinated individuals, compared to vaccination alone.” But he agrees that further work is needed to analyze the duration of protection conferred by infection against each of the variants, including Omicron.
How to explain this difference between natural and vaccinal immunities? In the event of a viral infection, the immune response operates in two main parts: the humoral and cellular responses. The first is that of antibodies, which circulate in the body and neutralize the virus before it injects its viral material into the cells to which it binds. The antibody response is directed against a key protein, Spike, which allows the virus to enter cells. “Here, vaccination does about the same thing as infection”, describes Jean-Daniel Lelièvre. Concretely, the maturation of memory B cells (B lymphocytes), which lead to the production of antibodies directed against the virus, “takes place better post-infection than post-vaccination. Ditto for the antibody response in the mucous membranes “, that is to say where the virus enters the body (the nose or the mouth), continues the immunologist, while the vaccines are administered by muscle.
The second, cellular response, which involves T lymphocytes, “is directed against the Spike protein but also against other proteins that are not present in the vaccine – M, N proteins, and others”, specifies Jean -Daniel Lelievre. In the event of infection, “the cellular response is therefore broader and, above all, lasts longer. If we take the example of SARS-CoV, close to the current SARS-CoV-2, the immune response persists for more than 20 years after the infection”.
Booster dose after infection? “No particular relevance”
There remains, for the two professors, the question of booster shots for people already infected. Is it really useful? Eric Caumes is formal: “Almost everyone caught Covid-19 last December and January. And people are not going to be revaccinated. Who said it couldn’t trigger an inappropriate immune response?” , he asks. Jean-Daniel Lelièvre sees “no particular relevance” in it. In most cases, immunity has been developed with a first dose of vaccine and then reactivated with infection. In general, this “being recent, it will therefore protect against all the variants currently available”, he adds. The government has also moved in this direction with its equivalence “one injection = one infection” decreed at the beginning of February. “Even if it is not entirely true and the message needs to be refined, it is going in the right direction”, judges the head of the infectious diseases department at Henri-Mondor hospital.
The paradigms of the current epidemic situation are, according to him, no longer those of a few months ago. “With the idea that the variants were not going to escape the humoral response as much, it was relevant to vaccinate the population quickly and widely, including infected people. Now, the collective immunity that we want reaching will be of lower quality since the antibody response against the variants is lower. Except for people infected with Omicron.” In other words, mass vaccination would regain its relevance with the arrival of new vaccines, or treatments, acting more on the transmission of the virus.
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Better understanding the infectivity of Covid-19 was one of the sub-goals of a UK pilot study, the team of which deliberately infected 36 healthy young adults – neither vaccinated nor having previously contracted the virus. This first “infectious challenge” aimed above all to demonstrate the feasibility and the absence of risk of this approach. Researchers would like this type of experience, over time, to accelerate the development of new treatments. But the first results, published in early February, did not revolutionize scientific knowledge of the disease.
