Researchers uncover a possible role of anti-idiotype antibodies in the long-term effect of COVID-19

The COVID-19 pandemicthat has caused more than the 256 million deaths, and more than 5 million injuries worldwide, has presented a challenge to scientists and medical professionals. Researchers are working to find effective therapies and vaccines as well as to better understand the long-term effects of the infection.

Although vaccines have been crucial in the control of pandemics, scientists are still trying to determine the mechanisms behind their effectiveness. This is especially true in light of the development of new variants of viruses and the rare vaccine adverse effects such as allergic reactions as well as heart inflammation (myocarditis) and blood-clotting (thrombosis).

Critical questions about the infection itself also remain. Around one in four COVID-19 patients experience persistent symptoms, even after recovering from the virus. These symptoms, referred to as “long COVID” and the vaccines’ off-target side effects are thought to be due to the immune response of a patient.

Today’s article in The New England Journal of Medicine provides an explanation for the various immune responses to the virus.

Antibodies mimicking the virus

Drawing upon classic immunological concepts, Murphy and Longo suggest that the Network Hypothesis by Nobel Laureate Niels Jerne could provide insights.

Jerne’s hypothesis provides a way for the immune system to regulate antibodies. It describes a chain reaction that the immune system initiates immune defense responses to an antigen (like virus). The same protective antibodies later could trigger a different immune response against themselves which can lead to their disappearance over time.

These secondary antibodies, called anti-idiotype antibodies, can be able to bind to and diminish the initial immune defense responses. They may mimic or behave like the antibody that was originally created. This could lead to adverse side effects.

Coronavirus and the immune system

SARS-CoV-2 virus, which causes COVID-19, contaminates the body with spike protein. It binds with the ACE2 receptor and allows entry into the cell. The immune system responds by releasing protective antibodies that bind to the virus that is invading, preventing or neutralizing its effects.

These protective antibodies can cause immune reactions using anti-idiotype antibodies as a result of downregulation. These anti-idiotype responses can eventually eliminate the initial protective antibodies, and may lead to limited effectiveness of anti-inflammatory therapies.

A fascinating aspect of newly developed anti-idiotype antibodies is that some of their structures can be mirror images of the antigen in the first place and behave as it does in binding to the same receptors the antigen from the virus binds. This binding can potentially cause unwanted actions and pathology, particularly over the long-term.”

William Murphy, UC Davis Vice Chair of Research and Distinguished Professor of Dermatology and Internal Medicine

The authors suggest that the anti-idiotype antibodies could target the same ACE2 receptors. By blocking or activating these receptors, they could affect various normal ACE2 functions.

“Given the importance of the functions and the wide distribution of ACE2 receptors on numerous cell types, it would be crucial to determine whether these regulatory immune responses could be responsible for some of the off-target or lasting effects being documented,” Murphy commented. These immune responses could also explain why long-lasting effects can persist for a long time after the virus infection has ended.

SARS-CoV-2 spike proteins are the principal antigens in COVID-19 vaccines. According to Murphy and Longo, current research studies on the immune response to these vaccines are primarily focused on the initial protective response and virus-neutralizing efficacy in comparison to other long-term aspects.

“With the immense impact of the pandemic and our reliance upon vaccines as our primary weapon,” Murphy said. “There is a huge need to conduct more basic research in science to better understand the complex immune system pathways. Murphy explained that this is due to the need to know how to maintain immune responses as well as the potential negative consequences of the various SARS-CoV-2 vaccines, particularly when boosters have been employed. These are testable questions that could be addressed in the lab and have been utilized in conjunction with other viral models.

Journal reference:

Murphy, W.J & Long, D.L., (2021) A Possible Role for Anti-idiotype Antibodies for SARS-CoV-2 Disease and Vaccination. New England Journal of Medicine.

Content Source:

Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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