immunological imprinting and why in the US and Europe they give a different vaccine than in Argentina

It was a routine checkup. The doctor told the man that he better wait and Covid vaccine in Europe, their vacation destination, because “the one they give is better.” In fact, the main laboratories are launching new doses against the coronavirus, not bivalent but now monovalent, the monovalent XBB. The reason for the swerve? A scientific challenge called immunological impression.

It should be noted that all those consulted for this note rejected the doctor’s suggestion cited above. Jorge Geffner, renowned immunologist and Senior Conicet researcher at the Institute for Biomedical Research in Retroviruses and AIDS (INBIRS), pointed out that, “considering that airplanes are a possible source of contagion, the advice is that if the person gets a booster, get vaccinated before travelingbe it the bivalent one or the Covid vaccine that is available.”

The medical representatives of the two main vaccine laboratories against SARS-CoV-2 stressed the same. Julia Spinardi, Medical and Scientific Affairs leader of Pfizer’s Emerging Markets Covid Unit, emphasized that, “to have protection against severe disease, it is never advisable to wait”. And according to Paula Pertzov, medical manager at Raffo, Moderna’s licensed laboratory in Argentina, “waiting is not being vaccinated”.

The world is running behind the capricious changes of the pandemic virus. The circle is vicious: hanging with reinforcements results in more hospitalizations. Hospitalizations, with greater chances of the virus mutating and generating genomic changes that escape the immune response generated by vaccines, given that hospitalized patients with severe Covid are like large reservoirs or viral multiplication plants.

Although the recommendation is to respect the recommended vaccination schedule, it is true that the new immunological tools that are emerging in the northern hemisphere. They arrive to these pampas with a delay of a few months..

Thus, even though bivalents protect against serious illness and even though in this wave of infections many feel they are “at the forefront” to receive these enhanced doses, from the point of view of scientific-technological evolution, the bivalent, in reality, was already.

Compared to times in the northern hemisphere, the doses adapted to the changes of the SARS-CoV-2 virus arrive later in Argentina for two reasons. The first is that, “being an American, It is necessary that the vaccine be approved in the local marketbefore requesting authorization from other regulatory agencies,” Spinardi explained from Pfizer.

The other reason is that, in practice, the drug regulatory agencies of the United States and Europe (FDA and EMA, respectively) function as “Lighthouses” of their global peers. In the case of Argentina, from the ANMAT.

In other words, a medicine that comes with the green light from these organizations (whose reputation is, in several senses – although not all -, “unquestionable”), although it will pass through the demanding local sieve, will initially have several beans to favor. It is worth remembering that, symbolically, the lack of those beans. It was part of the questioning of the Russian Sputnik V vaccine.

Pertzov, Moderna’s medical representative, explained that modifying the vaccine to adapt it to the current circulating virus takes about 90 days: “As with the flu, the FDA looks at the new circulating strains and asks the laboratories to update the vaccines. From now on, we will always be behind the virus, which permanently mutates”.

Spinardi agreed and explained that, in this case, “the process of adaptation to the Covid XBB variant was indicated by the World Health Organization and by the FDA and EMA. Once it is determined which variant to target, the messenger RNA platform allows the vaccine to be modified very quickly, in about 100 days. After that period, it will be completely ready from a production point of view.”

Both, Pfizer’s monovalent XBB and Moderna’s, They are being reviewed today by the ANMAT, an organization respected in the world but which, it is known, takes its time. However, the references estimated that, if everything goes smoothly (the ANMAT approves and the Argentine Health authorities recommend it), the monovalent XBB should be available to people by winter at the latest. Even before.

Is this a reason not to get vaccinated now and wait for it? Definitely not. To understand it, it is worth explaining why laboratories are returning to the monovalent vaccines.

The bivalents had been proposed as surpassers of the first generation of vaccinesgiven that they were directed against two targets, and not just one.

The objectives that were then set were, 1) to combat what everyone calls the “original variant”, or informally, “Wuhan”, and 2) to also focus on the genomic version of Covid that was widely considered “the” variant. which guaranteed the virus great contagiousness and less virulence. We must not forget that to continue multiplying, SARS-CoV-2 needs us alive…

We talk about Omicron, with his thousand and one facets (daughters and granddaughters of that variant) full of numbers and letters impossible to remember. From XBB to JN.1, to name just a couple.

However, now the laboratories decided to design a proposal that, they assure again, it is surpassing: monovalent vaccines (like the ones we used before the bivalent ones), but with the novelty that they do not target Wuhan but only against Omicron.

The explanation for this turn lies in the concept mentioned at the beginning of these lines: the so-called imprint immunological.

In English, “print” means “to print”, but also “to leave a mark”. “Impression“, in turn, means “imprint”, so that for imprint Immunological means the persistence of an imprint that directs immunity in a certain direction.

This is how Geffner explained it: “In one way or another, whether through infection or vaccines, almost everyone came into contact with the original Wuhan variant. What generates the phenomenon of imprint immunological? That, even when you get vaccinated with a dose based on one derived from Ómicron, you continue to ‘remember’ the original variant. The thing is, even if the variant is different, it will share reasons with Wuhan because both are, in short, SARS-CoV-2”.

“We say that they share epitopes, in reality,” explained Geffner, alluding to the technicality by which certain portions of a molecule manage to be recognized by immunological memory.

The problem generated by imprint is that if the immune system dominantly recognizes Wuhan, the protection with vaccine boosters will be reinforced in that direction, even when the vaccine contains a target (in the case of the bivalent ones, Ómicron).

So? The laboratories bet on remove the reference of the original variant of the new doses to improve the bias of the imprint immunological. Geffner believes it is a good plan, but stressed that, to date, there are no published studies that demonstrate superior effectiveness of these vaccines (compared to the previous ones), when it comes to avoiding hospitalizations.

“Everyone tries to torture the imprint immunological. And not only in Covid. This is a big problem in influenza as well. That’s why flu vaccines have an effectiveness that does not exceed 40% or 45%”he explained.

From the laboratories they point out that the new monovalents awaken a higher antibody titer, but Geffner clarified that “there is absolutely no published study that shows that the new monovalents are superior in preventing severe infection.” Because, “even when different levels of neutralizing antibodies are seen, that does not imply greater immunogenicity, and they are very subtle differences.”

“We always think of antibodies as the conclusive data, but protection for severe infection is not measured by antibodies as much as by the T lymphocyte response,” explained the scientist, and closed: “In this sense, the levels of effectiveness between some vaccines are not that different. “The indication continues to be to get vaccinated according to the recommended schedule with the doses that are available where you are.”