What is the Covid immune footprint? How does it affect reinfections and future vaccinations?

• Coronavirus Quarantines by Covid: the protocol does not oblige;

  responsibility to curb contagion, yes

• Health Why has Covid returned?

Now that another variant of

is out there and promises to be just as (if not more) contagious and immune-evading than BA.5, the debate over

for the next doses has reopened.

Continue with the current formulations based on the native virus originating in

(a strain very distant from Omicron), choose bivalent vaccines that mix the original formulation with

, or opt for vaccines that only include

?

And what

?

The first variant, BA.1, or the current BA.5, or the next?

A variable rarely talked about

Added to these considerations is

but that is essential to understand which way to go:

.

Immunological imprinting, also called

, says that the first Spike protein of

that a person encounters both by vaccination and by infection (therefore

against which the immune system is activated )

.

For example, a person who was infected in the first wave may not produce antibodies against other variants because the immune system "thinks" it is dealing with the "same virus."

But this reaction is subjective and does not always imply a weaker response.

It also happens with the flu

The phenomenon is known and has been described for the

,

, and others, and

, as shown in an article published a while ago in

.

This study also showed that neutralizing antibody responses against variants

and are highly variable depending on the infecting strain: sometimes this signature plays an advantage, other times it does not.

to future variants of the same pathogen (and this would explain the increasing reinfections), but it can sometimes enhance it.

You have to take into account the differences

The researchers note that immune responses to vaccination remain

from the new variants, but more than two years into the

, most people in the industrialized world have been infected or vaccinated against

and in different countries there are very different models of

depending on the different exposures, vaccinations and waves (for example in South Africa there was almost no BA.2 wave, but it went from BA.1 to BA .5 ).

Therefore,

and all of them are different.

The challenge is how to amplify population immunity in the right way:

must take into account the immune footprint and understand how to overcome the differences.

Antonella Viola, immunologist, full professor of General Pathology at the University of Padua explains: "It has been understood that vaccination, unlike infection, allows a broader immune response to be generated (because germinal centers are formed in the lymph nodes) than , therefore also allowing you to respond better to variants.However, it has also been understood that

with the boosts is

and lower for the increasingly different variants, which which indicates that there has been a clear imprint also given by vaccination".

The decisions

Meanwhile, last month the World Health Organization (WHO) said that

may be useful as

because they would broaden protection against different variants.

And on Tuesday, the US Food and Drug Administration (FDA) advisory board recommended including a component of the

BA.4/BA.5 subvariants in the planned booster for fall campaigns, but some Immunologists question whether these formulations will be more effective compared to another dose of the original Wuhan vaccine.

"In order to understand whether the boosters with the new vaccines work better against the new variants," adds the immunologist Antonella Viola, "we should compare the booster with the "classic" dose and the booster with the updated one, all other conditions being equal. "No differences were seen in the animals. So any vaccine is likely to work well and in the same way, precisely because the imprint has already existed. Of course, if Spike changed a lot, then it would make sense to update the vaccine because it would change the antigen. But no one expects this."

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