Immune imprinting makes some Covid-19 booster shots less effective, Chinese scientists find
- Study shows those who received three inactivated doses had lower antibody levels against Omicron variants
- Effectiveness also questioned in US as it prepares the way for annual vaccination
The finding highlighted the importance of considering a phenomenon called immune imprinting in vaccine design, the researchers said. Separately, immune imprinting has also been at the centre of a debate in the United States as it considers simplifying its vaccination programme.
Immune imprinting refers to the way people’s immune systems respond to a newly circulating strain by producing antibodies tailored to the first strain they encountered. In some cases, that could lead to a poorer ability to protect a person against a new strain of the virus.
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The scientists from Shanghai Jiao Tong University school of medicine compared 135 serum samples from three groups of Covid-19 patients: the unvaccinated, recipients of two doses of inactivated vaccine, and those who had three doses. They were all infected with the BA2 strain of the Omicron variant of the coronavirus, which was the prevailing strain during the outbreak in Shanghai early last year.
The researchers then tested the neutralising antibodies found in the samples against the original strain of Sars-CoV-2 – the virus that causes Covid-19 – as well as BA2 and two newer strains: BA4 and BA5.
In a letter published in the journal Cell Research on January 25, they said that while the vaccinated patients’ neutralising antibody levels against the original strain were comparable, those who had received three doses of vaccine had “significantly lower” antibody levels against the Omicron BA.2, BA.4 and BA.5 variants.
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They said the patients who received two or three doses all had mild symptoms, while some unvaccinated patients had developed severe symptoms.
“Our data suggest that repeated vaccination with inactivated virus vaccine back-boosts previous memory and dampens the immune response to a new antigenically related but distinct viral strain,” they wrote.
That could reflect the “original antigenic sin” that saw those infected with a new strain of flu virus develop a strong immune response to a strain they had previously been exposed to.
Immune imprinting has also been debated by scientists advising the US Food and Drug Administration on that country’s future vaccine policy.
Last week, an advisory panel endorsed an FDA proposal to make Covid-19 vaccinations annual, similar to flu shots.
A single formulation would be used for annual vaccination programmes, with the FDA proposing the use of bivalent vaccines that target the ancestral and Omicron strains.
However, some scientists questioned whether bivalent vaccines were a good choice because their effectiveness against the prevailing Omicron variants or future strains could be dampened by immunological memory induced by the ancestral strain.
In an article published in the New England Journal of Medicine on January 11, Paul Offit, a doctor in the infectious diseases division at the Children’s Hospital of Philadelphia, quoted two studies that found there was not much difference between a monovalent or bivalent booster in protecting against Omicron variants.
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“Why did the strategy for significantly increasing BA.4 and BA.5 neutralising antibodies using a bivalent vaccine fail? The most likely explanation is imprinting,” he wrote.
“The immune systems of people immunised with the bivalent vaccine, all of whom had previously been vaccinated, were primed to respond to the ancestral strain of Sars-CoV-2.”
Some scientists also questioned the need to have an annual shot given third shots already provided good protection against hospitalisation and severe diseases for most people.
Offit said boosters were “probably best reserved for the people most likely to need protection against severe disease – specifically, older adults, people with multiple coexisting conditions that put them at high risk for serious illness, and those who are immunocompromised”.
