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Home » Repeated COVID-19 vaccinations induce antibodies that neutralize variants and other viruses – WashU Medicine
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Repeated COVID-19 vaccinations induce antibodies that neutralize variants and other viruses – WashU Medicine

adminBy adminMay 17, 2024No Comments7 Mins Read
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Responses to updated vaccines are shaped by previous vaccines, but generate broadly neutralizing antibodies

matt miller

Healthcare workers received their first dose of the COVID-19 vaccine in December 2020. A study by researchers at Washington University School of Medicine in St. Louis found that repeated vaccinations with the latest version of a COVID-19 vaccine can accelerate the onset of infection. Antibodies that neutralize a wide range of variants of the virus that causes COVID-19 and related coronaviruses.

Although the global public health emergency caused by COVID-19 is over, the virus that caused it is still here, sending thousands of people to hospitals each week and emerging with depressing frequency. It is giving rise to a variety of mutant species. Due to the virus' remarkable ability to alter and evade immune defenses, the World Health Organization (WHO) recommends that COVID-19 vaccines be updated annually.

But some scientists worry that the remarkable success of the first COVID-19 vaccines could hurt the latest versions, undermining the usefulness of annual vaccination programs. Similar problems plague the annual influenza vaccine campaign. Immunity induced by one year of influenza vaccination may impede the immune response in subsequent years, reducing vaccine effectiveness.

A new study by researchers at Washington University School of Medicine in St. Louis helps answer this question. Unlike immunity to the influenza virus, prior immunity to SARS-CoV-2, the virus that causes coronavirus disease (COVID-19), does not inhibit subsequent vaccine responses. Rather, the researchers report, it promotes the development of broadly inhibitory antibodies.

The study, available online in the journal Nature, was conducted in people who received multiple COVID-19 vaccinations, first with vaccinations targeting the original variant, followed by booster shots and vaccinations targeting the variant. The study shows that those who received the latest vaccine (which received the latest vaccine) generated antibodies that can neutralize a wide range of SARS-CoV. – Two variants and also some distantly related coronaviruses. The study results show that regular revaccination against COVID-19, far from impeding the body's ability to recognize and respond to new variants, may actually protect it from new SARS-CoV- It suggests that people may gradually build up stocks of broadly neutralizing antibodies that protect them. So are the two variants and several other coronavirus species, including some that have not yet emerged to infect humans.

“The first vaccine an individual receives induces a strong primary immune response that shapes the response to subsequent infections and vaccinations, an effect known as imprinting,” said lead author Herbert S. Gasser. said Michael S. Diamond, MD, professor of medicine. “In principle, imprinting can be positive, negative, or neutral. In this case, we see strong positive imprinting, coupled with the development of cross-reactive neutralizing antibodies with significant broad activity. You can.”

Imprinting is a natural consequence of immunological memory mechanisms. The first vaccination triggers the development of memory immune cells. Receiving a second vaccination, which is very similar to the first, reactivates the memory cells that were induced by the first vaccine. These memory cells govern and shape the immune response to subsequent vaccines.

In the case of influenza vaccines, imprinting has negative effects. Antibody-producing memory cells crowd out new antibody-producing cells, and people produce relatively few neutralizing antibodies against new vaccine strains. However, imprinting can also be positive by promoting the development of cross-reactive antibodies that neutralize strains in both the first and subsequent vaccines.

To understand how imprinting affects the immune response to repeated COVID-19 vaccinations, Professor Diamond and colleagues, including first author graduate student Chie-Yu Lian, conducted a series of COVID-19 vaccinations. They studied antibodies in mice or people who were given a viral infection vaccine and booster. First the original, then the micron variant. Some of the human participants had been naturally infected with the virus that causes COVID-19.

The first question was about the strength of the imprinting effect. The researchers measured how many of the participants' neutralizing antibodies were specific for the original variant, the ohmicron variant, or both. They found that very few people had developed antibodies specific to omicron. This is a pattern that indicates strong imprinting from the first vaccination. But they also found few antibodies specific to the original variant. The majority of neutralizing antibodies cross-reacted with both.

The next question was how far-reaching the cross-reactivity effect was. Cross-reactive antibodies, by definition, recognize features shared by two or more variants. Some features are shared only by similar variants, while others are shared by all SARS-CoV-2 variants and even all coronaviruses. To assess the breadth of neutralizing antibodies, the researchers tested them against a range of coronaviruses, including two ohmicron lineages of the SARS-CoV-2 virus. Coronavirus from pangolins. SARS-1 virus that caused the SARS epidemic in 2002-2003. and Middle East Respiratory Syndrome (MERS) virus. This antibody neutralized all viruses except the MERS virus, which comes from other lineages in the coronavirus family tree.

Further experiments revealed that this surprising range was due to a combination of the original and mutant vaccines. People who received only vaccines targeting the original SARS-CoV-2 variant developed some cross-reactive antibodies that neutralized the pangolin coronavirus and SARS-1 virus, but at low levels. . However, after boosting with the Omicron vaccine, cross-reactive neutralizing antibodies against the two coronavirus species increased.

Taken together, this finding shows that regular revaccination with the latest COVID-19 vaccines against mutant strains can protect against not only the SARS-CoV-2 mutant strains contained in the vaccine, but also other SARS-CoV-2 This suggests that it may be possible to provide people with tools to fight off mutant strains as well. and related coronaviruses (including perhaps those that have not yet emerged).

“At the beginning of the COVID-19 pandemic, the world's population was immunologically immature, which is one of the reasons the virus was able to spread so quickly and cause so much damage. ” said Diamond, who is also a professor of molecular microbiology and medicine. Pathology and Immunology. “We don't know for sure whether getting the latest COVID-19 vaccine every year can protect people from emerging coronaviruses, but it's plausible. These data show that these cross-reactions If sexual antibodies do not decline rapidly, their levels will need to be tracked over time to know for sure, but they may offer some or substantial protection against the pandemic caused by the related coronavirus. It suggests that there is.

Liang CY, Raju S, Liu Z, Li Y, Arunkumar GA, Case JB, Scheaffer SM, Zost SJ, Acreman CM, Gagne M, Andrew SF, Carvalho dos Anjos DC, Foulds KE, McLellan JS, Crowe JE, Douek DC, Whelan SPJ, Elbashir SM, Edwards DK, Diamond MS. Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccine. Nature. May 15, 2024. DOI: 10.1038/s41586-024-07539-1

This research was supported by National Institutes of Health (NIH) grant number R01 AI157155. National Institute of Allergy and Infectious Diseases (NIAID) Influenza Research and Response Center, contract numbers 75N93021C00014 and 75N93019C00051. NIAID Vaccine Research Center. and a sponsored research agreement with Moderna. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH).

About the University of Washington School of Medicine

WashU Medicine is a world leader in academic medicine, including biomedical research, patient care, and education programs with 2,900 faculty members. The National Institutes of Health's (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% over the past seven years. Combined with institutional investments, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practices are consistently among the top five in the nation, with more than 1,900 faculty physicians practicing at 130 locations and on the medical staff of BJC Healthcare's Barnes-Jewish Hospital and St. Louis Children's Hospital. WashU Medicine has a storied history in MD/PhD training, recently investing $100 million in scholarships and curriculum updates for medical students, and offers training in all medical subspecialties, as well as physical therapy, occupational therapy, and audiology. We offer some of the best training programs in the field. and communication science.



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