Antibodies mimicking SARS-CoV-2 may explain long COVID and some rare vaccine side effects

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New Delhi: Around 260 million COVID-19 cases have been reported worldwide as of 25 November, with the pandemic claiming over 5 million lives globally. Scientists are working to create effective vaccines as well as trying to understand the long-term effects of COVID-19.

However, the effectiveness of vaccines is not fully understood. Vaccines also cause some rare side effects such as allergies, inflammation of the heart (myocarditis) and blood clotting (thrombosis). The side effects of the vaccine are believed to be due to the patient’s immune response.

Even after recovering from COVID-19, about one in four COVID-19 patients show symptoms. In a cured coronavirus patient, this condition is known as “long covid” when health problems persist even after testing negative, four or more weeks after infection.

In an article published Wednesday in The New England Journal of Medicine, two researchers present an explanation for the diverse immune responses to SARS-CoV-2 and vaccines. William Murphy, vice president of research at the University of California-Davis Health and Professor of Dermatology and Internal Medicine, and Dan Longo, professor of medicine at Harvard Medical School, are study authors.

SARS-CoV-2 . copying antibodies

The authors suggest that the work of Danish immunologist Niels Jarn, titled ‘Network Hypothesis’, may provide insight into how the immune system produces antibodies and reacts to the coronavirus.

Jrn, along with Georg K. Köhler and Cesar Milstein, were awarded the Nobel Prize in Physiology or Medicine in 1984 for their research on classic immunological concepts.

Jern’s hypothesis explains how the immune system controls the production of antibodies. An antibody response is a cascade reaction initiated by the immune system in response to an antigen (foreign body), such as a virus. The hypothesis states that protective antibodies may trigger a new antibody response on their own, leading to their disappearance.

These secondary antibodies are called anti-idiotype antibodies, and can bind to and terminate initial protective antibody responses. In other words, anti-idiotype antibodies reflect the original antigen itself, and result in an adverse effect.

When SARS-CoV-2 enters the body, its spike protein binds to the ACE2 receptor, and this allows the virus to enter the cell. In response to the invading virus, the immune system produces protective antibodies, which block or neutralize the effects of the virus by binding to it.

The authors said in the article that protective antibodies can cause an immune response with anti-idiotype antibodies, in the form of down-regulation (the process of reducing or suppressing the response to a stimulus). The initial protective antibody is cleared as a result of anti-idiotype reactions. This may result in limited efficacy of antibody-based therapies.

Murphy said an attractive aspect of the newly formed anti-idiotype antibodies is that some of their structures can be mirror images of the original antigen, and act like antigens, while the viral antigen binds to the same receptors, according to a statement. by UC-Davis. Compulsiveness can potentially lead to unwanted functions and distractions, especially over the long term, he explained.

The authors suggested that anti-idiotype antibodies could potentially target similar ACE2 receptors. Various normal ACE2 functions may be affected by the receptors being blocked or triggered.

Anti-idiotype antibodies may cause rare vaccine side effects

Murphy said it will be important to determine whether these regulatory immune responses are responsible for some of the off-target effects of vaccines, considering the fact that ACE2 receptors are widely distributed on many cells and serve important functions. Huh. Anti-idiotype responses may also explain why effects may occur long after the viral infection has passed, he said.

The SARS-CoV-2 spike protein is the primary antigen used in COVID-19 vaccines. According to Murphy and Longo, current research studies on antibody responses to these vaccines primarily focus on the initial protective responses and the efficacy of neutralizing viruses.

Murphy said more basic science research is desperately needed to understand the complex immunological pathways. It’s important to know what protective responses are going on, and to understand what causes potentially unwanted side effects of coronavirus infection and the different SARS-CoV-2 vaccine types, he said. As boosters are being given, it is necessary to know more about these reactions. Murphy said the good news is that these questions can be partially addressed in the laboratory, and have been used with other viral models.

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