WWith Covid-19 vaccines, the world is hoping to defeat the virus that causes the disease. But some scientists are increasingly concerned that future iterations of the vaccines will not always be as effective as they are today, due to our own biology.
The concern stems from a phenomenon known as the impression, sometimes called original antigenic sin, that probably affects how we respond to some pathogens.
In short, when your body first presents a specific threat – whether through infection or a vaccine – the definition of your immune system determines the virus and what immune weapons it needs to detect and protect against it in the future.
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This print may be helpful. In the H1N1 flu pandemic in 2009, elderly adults were protected by immune responses that they contracted in childhood more than half a century earlier through encounters with a related virus. But it can also interfere with your body’s ability to react against strains that have evolved from the one you were first exposed to.
In the case of Covid, some scientists are concerned that the immune system’s response to the vaccines now being deployed may leave an indelible mark, and that the next generation of products, which will be updated in response to emerging variants of the SARS-CoV -2, provides so much protection.
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Michael Worobey, who was involved in groundbreaking research on the impression of flu, said he was concerned that the reactions to the first generation of Covid-19 vaccines would be a ‘high watermark’ for the immune response of humans to these vaccinations.
“I think this is something we need to think about,” Worobey, a professor of evolutionary biology at the University of Arizona, told STAT. ‘We may see lower efficiency in five years’ time, if people still fail to recall the response to the first [SARS-2] antigen they saw. ”
Sarah Cobey, associate professor of computational biology at the University of Chicago, shares his concern. “As long as there is a competition between old antibody reactions and new antibody reactions … then it seems exactly the right environment to see these phenomena,” Cobey said.
“I can not think of a reason to limit to flu,” she added.
However, not everyone in the conversation is convinced that there will be a problem.
Vineet Menachery is an expert on coronavirus at the University of Texas Medical Branch in Galveston, one of the smaller communities of researchers who studied coronavirus before the Covid-19 pandemic. He noted that the SARS-2 ear protein – the protein that projects from the virus surface and carries the appearance of a crown – does not have as much winding space as the hemagglutinin proteins that sit on top of influenza viruses.
Both the peak and the hemagglutinin proteins are the means by which their respective viruses attach to the cells they are trying to infect; in the case of SARS-2 viruses, attachment takes place via a receptor known as ACE2. But influenza viruses mutate much faster than coronaviruses and they have much more room to change – mutation space, Menachery calls it – without compromising its functionality.
‘The changes we are seeing in the [SARS-2] variants are not whole pig changes, ”he said.
Imprint is one of the reasons why flu vaccines are not as protective as we would like. Influenza is a notorious form shift and the constant changes allow influenza viruses to protect the immune system caused by vaccination or previous infections. For example, people who first encountered H1N1 viruses never get as much protection against the H3N2 component of a flu shot as from the H1N1 part.
“Actually, I view original antigenic sin as a kind of hierarchy in the immune memory, which means you’re preferring to boost what you’ve seen before, at the expense of developing responses to the new things,” Cobey said. ‘It can increase the effectiveness of [Covid] vaccine forward. ”
Scott Hensley, sometimes an associate of Cobey’s, saw evidence of coronavirus in his research. An associate professor of microbiology at the University of Pennsylvania, Hensley and colleagues, were developing Covid-19 antibody tests in the early days of the pandemic. The work involves studying blood samples from people who contracted Covid. They compared the samples after infection with blood drawn from the same individuals before the pandemic.
When comparing the pre- and post-blood samples, they saw in the sample after infection a ‘dramatic’ increase in antibodies against one of the human coronaviruses, which is one of the causes of colds. It was a virus called OC43, which is in the same coronavirus family as SARS-2, as well as the viruses that cause SARS and MERS.
In other words, the Covid infection protected the immune system against another virus, which the immune system already knew.
Still, Hensley is not worried about impressions – or at least not among people vaccinated with mRNA vaccines. The very strong immune response generated by the Moderna and Pfizer BioNTech vaccines must outweigh any impact mutation as SARS-2. However, Hensley is concerned that people whose immunity to the virus is due to infection, not by vaccination, are having difficulty dealing with different viruses due to the impression effects.
David Topham, an immunologist at the University of Rochester Medical Center and director of the New York Influenza Center of Excellence, also envisions the possibility.
He noted that in the earliest stages of SARS-2 infection, the immune system has a response to a portion of the ear protein called S2. Later, the immune system focuses its attention on other parts of the peak, especially the portion of the protein that the virus attaches to cells that enter it, known as the receptor binding domain.
It is not yet known whether the early focus on S2 – which does not change much from virus to virus – will blind the immune system to the changes elsewhere in the peak protein. The updated vaccines try to teach the immune system to respond. to, Topham said.
Topham does not think this will be a problem with vaccines, due to the way the vaccines used are designed. The peak proteins they cause apparently hide the S2 region, he said. The immune system cannot detect something it does not see.
For people whose immunity is due to infection, Topham sees three possible scenarios. ‘This can be a problem because the immune cells that are specific for S2 surpass immune cells against other components of the ear protein that you really need to get protection. This may be unimportant because the answers to the other parts of the protein eventually catch up and that it does not matter. Or it may actually be an advantage because it makes the immune system improve faster. ”
Topham is not the only one to speculate that an original Covid vaccine with a booster that targets different viruses may actually lead to a stronger immune response.
“You can actually get a broader immune response,” said Florian Krammer, a professor of vaccination at the Icahn School of Medicine at Mount Sinai Hospital in New York.
Krammer used as an example by scientists from the Finnish Institute of Health and Welfare and the University of Turku about vaccination against H5N1 bird flu. H5N1 vaccine that does not contain additives – compounds that promote – causes weak immune responses. But in an article published in the journal Vaccine, the researchers reported that a priming and boosting regimen using two different H5N1 vaccines, made with different strains of the virus, caused a strong and prolonged response.
We may be able to figure out if this is going to be a problem sooner than you might think. Moderna is working with the National Institute of Allergy and Infectious Diseases – which helped design the original Covid vaccine – to test an updated version of the vaccine that focuses on the variant first noticed in South Africa, B. 1,351 th most common It seems that the immune responses caused by earlier versions of the virus may elude.
“The Phase 1 studies conducted by Moderna and NIAID … will provide immunogenicity data that will answer this question,” John Mascola, director of NIAID’s vaccination research center, said in an email to STAT. “The data directly related to the demand will therefore be available over the next weeks and months.”