How Covid’s ‘immune imprinting’ can help rethink vaccines?

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The increase in hospital admissions for Covid-19 caused by the BA.5 subvariant of the omicron, accompanied by the inability of vaccines to prevent reinfection, has led health policymakers to rethink their approach to booster doses.

Last week, U.S. regulators recommended changing the design of vaccines to produce a new booster targeting the micron — the first change in the composition of immunizers since their adoption in late 2020. Research on “immune imprinting” in that exposure to the virus through infection or vaccination determines an individual’s level of protection, now guides the debate over the composition of Covid-19 vaccines.

Immunologists say that after more than two years of the coronavirus pandemic, people acquired very different types of immunity to the Sars-Cov-2 virus, depending on the strain or combination of strains they were exposed to, leading to huge differences in the manifestation of Covid-19. 19 between individuals and countries.

“The effect is more subtle than ‘the more times you have it, the less protection you will have,'” said Professor Danny Altmann of Imperial College London, who is investigating the phenomenon with colleagues. “It’s more useful to think of it as a progressive attunement of a huge repertoire. Sometimes it will be beneficial for the next wave, sometimes not.”

What is ‘immune imprinting’?

After someone is exposed to a virus for the first time, through infection or vaccination, the immune system remembers its initial response in a way that usually weakens the response to future variants of the same pathogen, but can sometimes strengthen it. Proteins on the “spike”, which the virus uses to attach to human cells, play a key role.

“Our first encounter with the spike antigen, whether through infection or vaccination, shapes our subsequent pattern of immunity through ‘immune imprinting,'” said Professor Rosemary Boyton of Imperial College.

This pattern has been observed for many years in influenza and dengue viruses, when it was commonly called antigenic original sin. Studies are now showing that it also applies to Sars-Cov-2, although the effects are difficult to pin down, according to Altmann, who prefers the term “immune imprinting” to the biblical connotations of “original sin.”

A study of 700 UK healthcare professionals by Imperial College staff, published last month in the journal Science, found that the omicron infection had little or no beneficial effect in boosting any part of the immune system — antibodies, B cells or T cells—among people who have been “marked” with earlier variants of Sars-Cov-2.

“Omicron is far from a benign natural promoter of vaccine immunity, as we might have thought, but it is an especially stealthy immune evader,” Altmann said.

Vaccines used today were designed to fight the virus when it was detected in Wuhan, China, more than two years ago. They maintain high protection against serious illness and hospital admissions, but their effectiveness against transmission and mild infection rapidly diminishes, especially against the micron.

Understanding the effect of “immune imprinting” will help health officials decide which vaccines to use in future booster campaigns. Boyton said that “immune imprinting” has “important implications for vaccine design with lasting efficacy and dosing strategies.”

Does ‘immune imprinting’ help explain invasive infections?

Most people in the industrialized world have been infected or vaccinated against Covid – or both. The Schools Infection Survey of England, run by the London School of Hygiene and Tropical Medicine, last week released data showing that 99% of high school students tested positive for Covid antibodies from natural infection.

At this stage of the pandemic, the vast majority of Covid cases are reinfections in people whose immune defenses acquired by vaccines or previous infections are not sustained against the BA.4 and BA.5 subvariants of the omicron.

These “breakthrough” or invasive infections aren’t necessarily as mild as many people believe, said Ziyad Al-Aly, a clinical epidemiologist at Washington University in St Louis. He analyzed the health records of 34,000 people with Covid infections in the US Veterans Administration database, which provides healthcare to retired military personnel. The cumulative risk of serious damage to the heart, brain and lungs increased significantly with each repeated infection.

In another study, Al-Aly and colleagues found that while vaccines were good at preventing acute Covid-19, they were only 15% effective at preventing long-term Covid, which is defined as symptoms lasting 12 weeks or more after the outbreak. diagnosis of COVID-19. “Getting Covid, even among vaccinated people, seems almost inevitable these days,” he said.

Has ‘immune imprinting’ influenced vaccine discussions?

Some anti-vaccine people have included “immune imprinting” in their arguments, claiming that vaccines become less effective as the virus evolves — which immunologists emphatically reject.

“While our latest findings highlight clear concerns about the nature of omicron infection, vaccination remains effective against severe disease,” Altmann said. “Those who are eligible to receive a boost should be encouraged to do so.”

Professor Christian Drosten, a leading German virologist, said in an interview with Der Spiegel magazine that extending the interval between injections could help reduce the impact of “immune imprinting”.

“I suspect the effect [da vacinação] will improve the longer the interval from the previous vaccination,” he said.[Mas] It is still not really known what the interval between vaccinations should be.”

How did differing immunity affect vaccine decisions?

The World Health Organization said last month that micron-based vaccines could be beneficial as a booster because they would enhance protection against different variants.

And on June 28, the US Food and Drug Administration (FDA) advisory committee voted 19-2 for the inclusion of omicron genetic material in further booster doses.

“We’re trying to use every ounce of what we can from the predictive modeling and the data that’s emerging to try to get ahead of a virus that’s been very cunning,” said Peter Marks, director of the FDA’s Center for Biological Assessment and Research.

On Thursday (30), the agency recommended the inclusion of a component of the Omicron BA.4/BA.5 subvariants in a new dose for fall booster campaigns. But the agency did not advise a change in the existing vaccine for the first doses.

Moderna and BioNTech/Pfizer, the leading manufacturers of messenger RNA vaccines, presented laboratory data showing that their newer, omicron-targeted versions produce a potent antibody response against BA.4 and BA.5. But some immunologists remain uncertain whether it will be any more effective than receiving one more dose of the original Wuhan vaccine.

“Due to ‘immune imprinting,’ patterns of immunity against spike in different people and populations have become heterogeneous, complex and unpredictable,” said Boyton. “This is an argument for moving forward in a careful, thoughtful and evidence-based way.”

“The challenge for the next generation of Covid vaccines is to amplify the immune response to protect against future variants of concern.”

Translated by Luiz Roberto M. Gonçalves

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