What is “immune imprinting”? Is it making bivalent boosters less functional?

Countries like the United Kingdom and the United States have brought forward bivalent boosters since last September. These have been expected to safeguard against the coronavirus infection better, as compared to the original vaccine.

Everything seemed merry here until a few studies came forward to show that immune imprinting may be making the bivalent boosters less effective than everyone hoped for.

Earlier in January, the New England Journal of Medicine (NEJM) published two papers that said that bivalent boosters that were supposed to beat Covid-19 strains and the Omicron strains have failed to generate a greater amount of antibody responses as compared to the original mRNA vaccines.

Immune imprinting is considered the main reason behind this.

What is immune imprinting?

Immune imprinting is nothing but the body’s tendency to recur the immune response on the basis of the very first variant it came in contact with, whether through infection or vaccination, in case it encounters a fresh or a bit different variant of the very same pathogen.

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Findings so far!

It was in 1947 when the concept of immune imprinting came to light for the first time. Scientists observed that the bodies of individuals who were infected with flu previously and were vaccinated against the present circulating strain produced antibodies against the very first strain they had come into contact with. This had been found in a report brought forward in the journal Nature.

In those times, it was called  “original antigenic sin”. Today, however, the concept is termed imprinting.

In the years ahead, scientists have made a conclusion that this imprinting plays the role of a database for the immune system of the body. This database helps the body lead to a better response to repeat infections.

Once the body has come in contact with a virus for the very first time, the body gives rise to memory B cells. These cells circulate in the bloodstream. These then speedily produce antibodies just when the body is exposed to the same strain of virus again.

Isn’t it a good mechanism by the body? 

It is a beneficial mechanism, but not always. The issue arises when a variant of the virus that is just similar, but actually not identical to the virus comes in contact with the body. In these cases, the immune system of the body activates the memory B cells, rather than producing new B cells. Now, when these memory B cells are produced, they produce antibodies that bind to features observed in both strains, the old and the new ones. This is known as cross-reactive antibodies.

Now, the cross-reactive antibodies are not completely a waste; they do provide protection against the new strain. However, they are not as effective in safeguarding the body as compared to the ones produced by the B cells in the case when the body was encountered by the original virus for the very first time.

What do the recent studies have to say?

Researchers of the Columbia University Vagelos College of Physicians and Surgeons in New York underwent a study in which 40 participants were studied. These individuals have already got three shots of the monovalent vaccine (the original vaccine). In the experiment, 19 of these 40 participants were offered a booster (which was actually the fourth shot) of the monovalent (original) vaccine. The other 21 participants were given a booster of the new bivalent vaccine.

The experiment found that the bivalent boosters failed to elicit a discernibly greater virus-neutralizing peak antibody response in comparison with the original monovalent vaccines.

In another study, researchers from the Beth Israel Deaconess Medical Center in Boston observed immune responses in 15 individuals. These participants had got the original monovalent boosters, while in another 18 participants, the response of bivalent boosters had been recorded.

As a result, it was observed that the median BA.5 (Omicron) neutralizing antibody titer was similar to post-monovalent and bivalent mRNA boosting, along with a modest trend inclining toward the bivalent booster by a factor of 1.3.

These two studies and more point out the fact that immune imprinting might be creating a barrier to the effectiveness of bivalent vaccines. 

In 2022, Professor Rosemary Boyton, along with her team, did a study at the Imperial College London on  the same issue. The professor and the team found that the Omicron infection had negligible or no advantageous effect of boosting any of the immune system’s parts. The study comprised over 700 participants. These immune systems of these 700 participants had been imprinted with older coronavirus variants.

David Ho, authors of the Columbia University research had made a statement in an interview saying that they were somewhere expecting the results they found. In vaccinology, there is a phenomenon called as immunological imprinting the phenomenon means that the “immune memory preferentially sees what is has seen before.”

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If the bivalent boosters aren’t as effective as the monovalent ones, then is it okay to skip them?

No. David Ho clarified the doubt by saying that even if boosters aren’t as good as the original ones, people still should get their bivalent boosters.

What did the World Health Organization (WHO) say?

The World Health Organization (WHO) cautioned last year by saying, “The bulk of benefits is from the provision of a booster, irrespective of whether it is a monovalent or bivalent vaccine.”

As suggested by scientists, irrespective of the type, vaccines against coronavirus are extremely important in keeping the serious illness at bay. However, currently, the need of the hour is to introduce a vaccine that has the ability to combat immune imprinting, while also fighting virus transmission.

Is there a way around dealing with immune imprinting?

At present, there are many studies that are looking for a method to circumvent immune imprinting. A few scientists have suggested that nasal vaccines might prove to be better at stopping infections as compared to injected vaccines. 

These scientists are of the view that the mucous membranes would offer stronger protection, regardless of whether they carry some imprints of previous encounters.

Many researchers all over the world are also aiming to figure out if coronavirus vaccines could be spaced out on a yearly basis, and if this could help circumvent the issue of immune imprinting.

David Ho also expressed in an interview that a considerable amount of effort is directed toward developing pan-sarbecovirus vaccines. These vaccines will safeguard against all variants causing COVID. These vaccines may even shield us against SARS and other viruses. However, one should not expect the development of such a vaccine overnight. The efforts will take time to bear fruits.

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