University of California And Harvard Scientists Claim Anti-idiotype Antibodies Produced In SARS-CoV-2 Infection And Vaccination Causes Variety Of Health Issues!
A new study by researchers from University of California-Davis has discovered that anti-idiotype antibodies produced in SARS-CoV-2 infection and vaccination causes a multitude of health conditions associated with Long COVID and vaccine side effects.
Anti-idiotype antibodies are antibodies that bind to the variable region of another antibody.
Anti-idiotype (or “Ab2”) antibodies binding to the original receptor on normal cells therefore have the potential to mediate profound effects on the cell that could result in pathologic changes, particularly in the long term ie long after the original antigen itself has disappeared. The ‘normal workings’ of the immune system can also end up being disrupted.
For SARS-CoV-2 infection, attention centers on the spike (S) protein and its critical use of the angiotensin-converting–enzyme 2 (ACE2) receptor to gain entry into the cell. Given its critical role in regulating angiotensin responses, many physiological effects can be influenced by ACE2 engagement.
The S protein itself has a direct effect on suppressing ACE2 signaling by a variety of mechanisms and can also directly trigger toll-like receptors and induce inflammatory cytokines.
responses may affect ACE2 function, resulting in similar effects. However, preclinical and clinical assessments of antibody responses to SARS-CoV-2 vaccines have focused solely on Ab1 responses and virus-neutralizing efficacy. The delineation of potential anti-idiotype responses has inherent difficulties because of the polyclonal nature of responses, dynamic kinetics, and the concurrent presence of both Ab1 and Ab2 antibodies. Furthermore, ACE2 expression within cells and tissues can be variable. The different vaccine constructs (RNA, DNA, adenoviral, and protein) are also likely to have differential effects on Ab2 induction or in the mediation of vaccine effects that differ from responses to infection. Some off-target effects may not be directly linked to Ab2 responses.
The association of thrombotic events with some SARS-CoV-2 vaccines in young women and the etiologic role of anti–platelet factor 4–polyanion antibodies may be the result of the adenoviral vector. However, the reported occurrence of myocarditis after vaccine administration bears striking similarities to the myocarditis associated with Ab2 antibodies induced after some viral infections. Ab2 antibodies could also mediate neurologic effects of SARS-CoV-2 infection or vaccines, given the expression of ACE2 on neuronal tissues, the specific neuropathologic effects of SARS-CoV-2 infection, and the similarity of these effects to Ab2-mediated neurologic effects observed in other viral models.
The study team said that it would therefore be prudent to fully characterize all antibody and T-cell responses to the virus and the vaccines, including Ab2 responses over time. Using huACE2 transgenic mice and crossing them with strains that are predisposed to autoimmunity or other human pathologic conditions can also provide important insights. An understanding of potential Ab2 responses may also provide insights into Ab1 maintenance and efficacy and into the application of antibody-based therapeutic agents. However, much more basic science research is needed to
determine the potential role idiotype-based immunoregulation of both humoral and cell-mediated responses may play both in antiviral efficacy and in unwanted side effects of both SARS-CoV-2 infection and the vaccines that protect us from it.
The study findings were published in the peer reviewed journal” the New England Journal of Medicine. https://www.nejm.org/doi/10.1056/NEJMcibr2113694
To date, the COVID-19 pandemic has infected almost 260 million people globally and caused more than 5.18 million deaths. These figures are expected to increased exponentially in coming weeks.
The pandemic has challenged scientists and those in the medical field and every day we are discovering new things about the virus and the disease it causes. To make things even more complicated, the SARS-CoV-2 is mutating rapidly and they are so many new variants and sub-variants emerging with different characteristics and also different pathogenesis patterns.
Scientists are working to find effective vaccines and therapies, as well as understand the long-term effects of the infection.
Although the vaccines have been critical in pandemic control, researchers are still learning how and how well they work. This is especially true with the emergence of new viral variants and the rare vaccine side effects like allergic reactions, heart inflammation (myocarditis) and blood-clotting (thrombosis).
Key critical questions about the infection itself also remain. Approximately one in four COVID-19 patients have lingering symptoms, even after recovering from the virus. These symptoms, known as "long COVID," or PASC (Post-acute Sequelae of COVID-19 and the vaccines' off-target side effects are thought to be due to a patient's immune response.
The study team comprising of the University of California-Davis Vice Chair of Research and Distinguished Professor of Dermatology and Internal Medicine Dr William Murphy and Professor of Medicine at Harvard Medical School Dr Dan Longo present a possible explanation to the diverse immune responses to the virus and the vaccines.
Both Dr Murphy and DR Longo drawing upon classic immunological concepts, suggest that the Network Hypothesis by Nobel Laureate Dr Niels Jerne might offer insights.
Dr Jerne's hypothesis details a means for the immune system to regulate antibodies. It describes a cascade in which the immune system initially launches protective antibody responses to an antigen (like a virus). These same protective antibodies later can trigger a new antibody response toward themselves, leading to their disappearance over time.
It was noted that these secondary antibodies, called anti-idiotype antibodies, can bind to and deplete the initial protective antibody responses. They have the potential to mirror or act like the original antigen itself. This may result in adverse effects.
Typically, when SARS-CoV-2, the virus causing COVID-19, enters the body, its spike protein binds with the ACE2 receptor, gaining entry to the cell. The immune system responds by producing protective antibodies that bind to the invading virus, blocking or neutralizing its effects.
However, as a form of down-regulation, these protective antibodies can also cause immune responses with anti-idiotype antibodies.
Alarmingly, over time, these anti-idiotype responses can clear the initial protective antibodies and potentially result in limited efficacy of antibody-based therapies.
Dr Murphy told Thailand Medical News
, "A fascinating aspect of the newly formed anti-idiotype antibodies is that some of their structures can be a mirror image of the original antigen and act like it in binding to the same receptors that the viral antigen binds. This binding can potentially lead to unwanted actions and pathology, particularly in the long term.”
The study team suggest that the anti-idiotype antibodies can potentially target the same ACE2 receptors. In blocking or triggering these receptors, they could affect various normal ACE2 functions.
Dr Murphy added, "Given the critical functions and wide distribution of ACE2 receptors on numerous cell types, it would be important to determine if these regulatory immune responses could be responsible for some of the off-target or long-lasting effects being reported. These responses may also explain why such long-term effects can occur long after the viral infection has passed."
In the case of COVID-19 vaccines, the primary antigen used is the SARS-CoV-2 spike protein. According to Dr Murphy and Dr Longo, current research studies on antibody responses to these vaccines mainly focus on the initial protective responses and virus-neutralizing efficacy, rather than other long-term aspects.
Dr Murphy stressed, "With the incredible impact of the pandemic and our reliance on vaccines as our primary weapon, there is an immense need for more basic science research to understand the complex immunological pathways at play. This need follows to what it takes to keep the protective responses going, as well as to the potential unwanted side effects of both the infection and the different SARS-CoV-2 vaccine types, especially as boosting is now applied. The good news is that these are testable questions that can be partially addressed in the laboratory, and in fact, have been used with other viral models."
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