The Ineffectiveness of New Covid-19 Boosters: Understanding Immune Imprinting

As the world continues to grapple with the ongoing Covid-19 pandemic, countries have been rolling out variant-specific or bivalent boosters in an effort to provide better protection against the virus. However, recent studies have shown that a phenomenon known as immune imprinting may be making these new boosters far less effective than anticipated. In this article, we’ll take a closer look at what immune imprinting is, and how it may be impacting the effectiveness of the new Covid-19 boosters.

What is Immune Imprinting?

  • Immune imprinting is the body’s tendency to repeat its immune response based on the first variant of a pathogen it encountered, whether through infection or vaccination. This phenomenon was first observed in 1947, when scientists noted that people who had previously had the flu, and were then vaccinated against the current circulating strain, produced antibodies against the first strain they had encountered. At the time, it was called “original antigenic sin” but today, it’s commonly known as imprinting.
  • Over the years, scientists have realized that imprinting acts as a database for the immune system, helping it put up a better response to repeat infections. When our body is exposed to a virus for the first time, it produces memory B cells that circulate in the bloodstream and quickly produce antibodies whenever the same strain of the virus infects again.
  • The problem occurs when a similar, not identical, variant of the virus is encountered by the body. In such cases, the immune system, rather than generating new B cells, activates memory B cells, which in turn produce “antibodies that bind to features found in both the old and new strains, known as cross-reactive antibodies,” according to a report in the journal Nature. Although these cross-reactive antibodies do offer some protection against the new strain, they aren’t as effective as the ones produced by the B cells when the body first came across the original virus.

The Findings of Recent Studies

  • Two papers published earlier in January in the New England Journal of Medicine (NEJM) pointed out that bivalent boosters—made to counter both the Omicron strains and the original Covid-19 strain—don’t generate significantly greater antibody responses than an additional dose of the original mRNA vaccines.
  • In the first study, done by the researchers of the Columbia University Vagelos College of Physicians and Surgeons in New York, participants were 40 individuals who had already received three shots of the original or monovalent vaccine. 19 of them were given a booster (fourth shot) of the original vaccine while 21 received a booster of the new bivalent vaccine. It was observed that the bivalent boosters “did not elicit a discernibly superior virus-neutralizing peak antibody response as compared with boosting with the original monovalent vaccines” across all coronavirus strains tested.
  • In the second study, researchers of the Beth Israel Deaconess Medical Center in Boston evaluated immune responses in 15 participants who had received the original monovalent boosters, and in 18 participants who had received the bivalent boosters. It was found that “median BA.5 (Omicron) neutralizing antibody titer was similar after monovalent and bivalent mRNA boosting, with a modest trend favoring the bivalent booster by a factor of 1.3.”
  • The findings of both studies suggested immune imprinting might be posing a hurdle in the success of the bivalent or variant-specific vaccines. Earlier, a 2022 study done by Professor Rosemary Boyton and her team at Imperial College London observed that Omicron infection “had little or no beneficial effect of boosting any part of the immune system” among the 700 participants, who had been imprinted with older coronavirus variants.

The Implications of Immune Imprinting

  • These findings have significant implications for the ongoing efforts to combat the Covid-19 pandemic. It suggests that the new variant-specific or bivalent boosters may not be as effective as hoped in providing protection against the Omicron strains of the virus. This is because the immune system may be relying on the cross-reactive antibodies produced by the memory B cells, rather than generating new B cells specific to the new strain.
  • This also highlights the importance of ongoing monitoring and research on the different Covid-19 variants. As new variants continue to emerge, it’s crucial to understand how the immune system responds to them and how best to develop vaccines and boosters that can provide effective protection against them.


The ongoing Covid-19 pandemic has highlighted the importance of understanding the complex mechanisms of the immune system and how it responds to different viruses. The phenomenon of immune imprinting is a reminder that our understanding of the virus and its variants is still evolving, and that ongoing research is needed to ensure we have the best tools to combat the pandemic. The recent studies suggest that the new variant-specific or bivalent boosters may not be as effective as hoped in providing protection against the Omicron strains of the virus, highlighting the need for ongoing monitoring and research on the different Covid-19 variants.

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