- Class switch towards spike protein-specific IgG4 antibodies after SARS-CoV-2 mRNA vaccination depends on prior infection history | Scientific Reports Nature.com
- Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation Science
- Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination The Lancet
- Detection of different variants of SARS-CoV-2 RNA (genome) on inanimate surfaces in high-touch public environmental surfaces | Scientific Reports Nature.com
- Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers Nature.com
- View Full Coverage on Google News
Tag Archives: antibodies
Long COVID: Cedars-Sinai Researchers Find COVID-19 Vaccine Produces Antibodies Far Longer Than Expected – SciTechDaily
- Long COVID: Cedars-Sinai Researchers Find COVID-19 Vaccine Produces Antibodies Far Longer Than Expected SciTechDaily
- No association between out-of-hospital cardiac arrest and COVID-19 vaccination, show study Medical Xpress
- Study Finds No Link To The COVID Vaccine & Sudden Cardiac Arrest So There Goes That Argument Pedestrian.TV
- No truth to anti-vaxxers’ claims linking COVID vaccine and sudden cardiac arrest: study Sydney Morning Herald
- Covid vaccines pose minimal risk of blood clots, says study Interesting Engineering
- View Full Coverage on Google News
Scientists find human antibodies that can block multiple coronaviruses including SARS-CoV-2 – Medical Xpress
- Scientists find human antibodies that can block multiple coronaviruses including SARS-CoV-2 Medical Xpress
- SARS-CoV-2 BA.1 and BA.2 breakthrough infections likely protect against BA.4 infection News-Medical.Net
- Human antibodies found that can block multiple coronaviruses: Study timesofindia.com
- Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials The Lancet
- New cell-based assay shown to rapidly profile drug resistance to three widely used SARS-CoV-2 main protease inhibiting drugs News-Medical.Net
- View Full Coverage on Google News
Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials – The Lancet
- Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials The Lancet
- Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants Nature.com
- Can the gut microbiota and metabolome explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients? News-Medical.Net
- SARS-CoV-2 in animals: susceptibility of animal species, risk for animal and public health, monitoring, prevention and control European Centre for Disease
- View Full Coverage on Google News
An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination – Science
- An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination Science
- Reassuring Findings on Bivalent COVID Booster in Hemodialysis Patients Medpage Today
- Bivalent and monovalent mRNA boosters induce similar antibody response against Omicron subvariants News-Medical.Net
- Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose Science
- Immunologic Effect of Bivalent mRNA Booster in Patients Undergoing Hemodialysis | NEJM nejm.org
- View Full Coverage on Google News
Free spike proteins in the blood appear to play a role in myocarditis post-COVID mRNA vaccine
Following the large-scale rollout of the messenger ribonucleic acid (mRNA) vaccines developed to prevent infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptomatic coronavirus disease 2019 (COVID-19), several cases of myocarditis were reported, mostly among healthy young people.
A recent study published in the journal Circulation examines the immunological picture in this scenario, looking for clues to the etiology of this rare and potentially serious complication.
Study: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Image Credit: Design_Cells / Shutterstock
Introduction
The development of myocarditis following mRNA vaccination is rare, occurring in <2 per 100,000 individuals. It remains an unpredictable mysterious occurrence. Some have suggested that it is linked to the overproduction of antibodies or abnormal immune responses.
Autoantibody production due to polyclonal B cell activation and proliferation has also been suggested, as has immune complex formation and inflammation. Finally, some think that cardiac antigens closely resembling the spike protein are targeted by autoantibodies formed as a result of molecular mimicry.
The immune response to these vaccines in these patients needs to be better understood in order to determine why and how it happens. It is imperative to study the role of male hormones since young male patients are most often affected.
The researchers in this study looked at blood samples from 16 myocarditis patients, confirmed to have high levels of serum cardiac troponin T. All developed myocarditis after receiving the COVID-19 vaccine, typically within a week of the second dose. However, a few became sick after the first dose or booster dose. Over 80% were male.
They were studied by antibody profiling, including antibodies to the virus, autoantibodies or antibodies to the virome, and the analysis of T cells specifically directed against the virus. In addition, cytokine and antigen profiles were determined. These measurements were compared with those of 45 vaccinated controls, who were of similar age and health.
What did the study show?
All subjects and controls showed a rise in anti-spike antibodies and antibodies to the receptor binding domain (RBD), of all immunoglobulin (Ig) subclasses, IgA, IgM, and IgG. Functional differences were not perceived either, with Fc effector functions being similar in both categories. In short, all vaccinated individuals showed evidence of a protective immune response against the virus.
“We found no indication that a specific antibody response is associated with myocarditis.”
Additionally, these patients did not show evidence of increased autoantibody production or antibody production against other respiratory pathogens that differed in magnitude or range from the controls.
T cells of all relevant subtypes, including naïve, memory, and effector memory T cells, showed similar distributions in both groups. T cells also showed similar proportions of spike-specific memory CD4 T cells and activated CD4 and CD8 T cells. The only exceptions were the observation of small elevations in effector memory cells and PD-1-expressing bulk CD4 T cells in the myocarditis group.
The findings indicated that antibody and T-cell responses could not distinguish between post-vaccine myocarditis subjects and vaccinated controls. The only significant difference was a slight elevation in cytokine production in the former.
The exciting difference was the high level of circulating full-length spike protein in the plasma of myocarditis patients, at a mean of ~34 pg/mL. Furthermore, the protein was not bound to antibodies and remained detectable for up to three weeks from the vaccination date. In contrast, controls did not have free spike protein in their blood.
This difference could not be attributed to poor neutralizing capacity in the myocarditis group, which showed comparable neutralization relative to the control group.
Concordantly, myocarditis patients had cytokine release patterns resembling those found in multisystem inflammatory syndrome in children (MIS-C). This might indicate that the innate immune response was overactive, leading to elevations in interleukin (IL)-8, IL-10, IL-4, IL-6, tumor necrosis factor (TNF)-α, and interferon (INF)-γ relative to healthy controls. IL-8 was most closely associated with raised cardiac troponin T and antigen levels.
Alongside, leukocytes, especially neutrophils, were at higher mean levels in this group than controls, though still within normal range.
What are the implications?
The study shows that the immunological response elicited by the mRNA vaccine was very similar in those who developed post-vaccination myocarditis and others. In other words, myocarditis could not be associated with abnormal autoantibodies, viral infections other than SARS-CoV-2, or excessive production of antibodies elicited by the mRNA vaccine.
In vaccinated patients, infection with the virus was not likely to be a cause or contributing factor for myocarditis since anti-Nucleoprotein IgG was not found in these patients.
In contrast to controls, the finding of high levels of unbound full-length spike protein in myocarditis patients may point to the mechanism by which this condition arises. Similarly, MIS-C patients had circulating SARS-CoV-2 antigens.
The spike protein appears to evade immune antibodies found at normal levels in these patients, with adequate functional and neutralization capacity. The spike may damage the cardiac pericytes or endothelium, perhaps by reducing the expression of the angiotensin-converting enzyme 2 (ACE2), reducing nitric oxide production in the endothelium, or activating inflammation via integrins, causing the endothelium to become abnormally permeable.
“Thus, the spike antigen itself, which evades antibody recognition rather than invoking immune hyperactivation, may contribute to myocarditis in these individuals.”
This finding does not amount to evidence against the benefit of vaccination with these vaccines, which effectively protect against severe COVID-19 outcomes. Therefore, current vaccine recommendations are unlikely to be altered due to these results.
“Understanding the immunopathological mechanisms associated with postvaccine myocarditis will help improve safety and guide the development of future coronavirus disease 2019 (COVID-19) vaccines. These findings also suggest that administration of anti-spike antibodies, if spike antigenemia is detected, could potentially prevent or reverse postvaccine myocarditis.”
Free spike proteins in the blood appear to play a role in myocarditis post-COVID mRNA vaccine
Following the large-scale rollout of the messenger ribonucleic acid (mRNA) vaccines developed to prevent infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptomatic coronavirus disease 2019 (COVID-19), several cases of myocarditis were reported, mostly among healthy young people.
A recent study published in the journal Circulation examines the immunological picture in this scenario, looking for clues to the etiology of this rare and potentially serious complication.
Study: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Image Credit: Design_Cells / Shutterstock
Introduction
The development of myocarditis following mRNA vaccination is rare, occurring in <2 per 100,000 individuals. It remains an unpredictable mysterious occurrence. Some have suggested that it is linked to the overproduction of antibodies or abnormal immune responses.
Autoantibody production due to polyclonal B cell activation and proliferation has also been suggested, as has immune complex formation and inflammation. Finally, some think that cardiac antigens closely resembling the spike protein are targeted by autoantibodies formed as a result of molecular mimicry.
The immune response to these vaccines in these patients needs to be better understood in order to determine why and how it happens. It is imperative to study the role of male hormones since young male patients are most often affected.
The researchers in this study looked at blood samples from 16 myocarditis patients, confirmed to have high levels of serum cardiac troponin T. All developed myocarditis after receiving the COVID-19 vaccine, typically within a week of the second dose. However, a few became sick after the first dose or booster dose. Over 80% were male.
They were studied by antibody profiling, including antibodies to the virus, autoantibodies or antibodies to the virome, and the analysis of T cells specifically directed against the virus. In addition, cytokine and antigen profiles were determined. These measurements were compared with those of 45 vaccinated controls, who were of similar age and health.
What did the study show?
All subjects and controls showed a rise in anti-spike antibodies and antibodies to the receptor binding domain (RBD), of all immunoglobulin (Ig) subclasses, IgA, IgM, and IgG. Functional differences were not perceived either, with Fc effector functions being similar in both categories. In short, all vaccinated individuals showed evidence of a protective immune response against the virus.
“We found no indication that a specific antibody response is associated with myocarditis.”
Additionally, these patients did not show evidence of increased autoantibody production or antibody production against other respiratory pathogens that differed in magnitude or range from the controls.
T cells of all relevant subtypes, including naïve, memory, and effector memory T cells, showed similar distributions in both groups. T cells also showed similar proportions of spike-specific memory CD4 T cells and activated CD4 and CD8 T cells. The only exceptions were the observation of small elevations in effector memory cells and PD-1-expressing bulk CD4 T cells in the myocarditis group.
The findings indicated that antibody and T-cell responses could not distinguish between post-vaccine myocarditis subjects and vaccinated controls. The only significant difference was a slight elevation in cytokine production in the former.
The exciting difference was the high level of circulating full-length spike protein in the plasma of myocarditis patients, at a mean of ~34 pg/mL. Furthermore, the protein was not bound to antibodies and remained detectable for up to three weeks from the vaccination date. In contrast, controls did not have free spike protein in their blood.
This difference could not be attributed to poor neutralizing capacity in the myocarditis group, which showed comparable neutralization relative to the control group.
Concordantly, myocarditis patients had cytokine release patterns resembling those found in multisystem inflammatory syndrome in children (MIS-C). This might indicate that the innate immune response was overactive, leading to elevations in interleukin (IL)-8, IL-10, IL-4, IL-6, tumor necrosis factor (TNF)-α, and interferon (INF)-γ relative to healthy controls. IL-8 was most closely associated with raised cardiac troponin T and antigen levels.
Alongside, leukocytes, especially neutrophils, were at higher mean levels in this group than controls, though still within normal range.
What are the implications?
The study shows that the immunological response elicited by the mRNA vaccine was very similar in those who developed post-vaccination myocarditis and others. In other words, myocarditis could not be associated with abnormal autoantibodies, viral infections other than SARS-CoV-2, or excessive production of antibodies elicited by the mRNA vaccine.
In vaccinated patients, infection with the virus was not likely to be a cause or contributing factor for myocarditis since anti-Nucleoprotein IgG was not found in these patients.
In contrast to controls, the finding of high levels of unbound full-length spike protein in myocarditis patients may point to the mechanism by which this condition arises. Similarly, MIS-C patients had circulating SARS-CoV-2 antigens.
The spike protein appears to evade immune antibodies found at normal levels in these patients, with adequate functional and neutralization capacity. The spike may damage the cardiac pericytes or endothelium, perhaps by reducing the expression of the angiotensin-converting enzyme 2 (ACE2), reducing nitric oxide production in the endothelium, or activating inflammation via integrins, causing the endothelium to become abnormally permeable.
“Thus, the spike antigen itself, which evades antibody recognition rather than invoking immune hyperactivation, may contribute to myocarditis in these individuals.”
This finding does not amount to evidence against the benefit of vaccination with these vaccines, which effectively protect against severe COVID-19 outcomes. Therefore, current vaccine recommendations are unlikely to be altered due to these results.
“Understanding the immunopathological mechanisms associated with postvaccine myocarditis will help improve safety and guide the development of future coronavirus disease 2019 (COVID-19) vaccines. These findings also suggest that administration of anti-spike antibodies, if spike antigenemia is detected, could potentially prevent or reverse postvaccine myocarditis.”
New COVID Subvariant Resistant to All Therapeutic Antibodies
Researchers discovered that neither individual antibodies nor antibody cocktails were able to neutralize the Omicron subvariant BQ.1.1.
The findings indicate that new antibody therapies must be developed.
Are the currently approved antibody therapies used to treat patients who have a higher risk of developing severe
The Omicron subvariants BA.1, BA.4, BA.5 as well as Q.1.1 have a high number of mutations in the spike protein. Some of these mutations are escape mutations that allow the virus to escape neutralization by antibodies. In addition, resistance to biotechnologically produced antibodies, which are administered to high-risk patients as a preventive measure or as therapy for a diagnosed SARS-CoV-2 infection, is also developing. Omicron sub-lineage BQ.1.1 is the first variant resistant to all antibody therapies currently approved by the EMA (European Medicines Agency) and/or FDA (US Food and Drug Administration). Credit: Markus Hoffmann, Deutsches Primatenzentrum
However, certain SARS-CoV-2 variants, notably the Omicron variant, avoid neutralizing antibodies and cause symptomatic infections even in vaccinated or convalescent individuals due to mutations in the spike protein. This is known as immune evasion, and it poses a hazard to high-risk populations including the elderly and people with weakened immune systems, for example, due to illness or medication.
They often fail to develop an immune response sufficient for protection from severe disease, even after full vaccination. To protect high-risk patients, biotechnologically produced antibodies are administered as a preventive measure or as an early therapy upon confirmed SARS-CoV-2 infection. Mutations in the spike protein of different SARS-CoV-2 variants confer resistance to individual antibody therapies. Therefore, it is important to regularly monitor whether therapeutic antibodies continue to be effective against currently circulating viral variants.
A team of researchers from the Infection Biology Unit at the German Primate Center – Leibniz Institute for Primate Research and the Division of Molecular Immunology at the Friedrich-Alexander-University Erlangen-Nürnberg has investigated how efficiently approved antibody therapies inhibit the currently circulating Omicron subvariants. The researchers found that the Omicron subvariant BQ.1.1, which is on the rise worldwide, is resistant to all available antibody therapies.
“For our studies, we mixed non-propagating viral particles carrying the spike protein of selected viral variants with different dilutions of the antibodies to be tested and subsequently measured the amount of antibody needed to inhibit infection of cell cultures. In total, we tested twelve individual antibodies, six of which are approved for clinical use in Europe, and four antibody cocktails” explains Prerna Arora, lead author of the study.
The researchers found that the Omicron subvariant BQ.1.1 could not be neutralized by either individual antibodies or antibody cocktails. In contrast, the currently predominant Omicron subvariant BA.5 was still neutralized by one approved antibody and two approved antibody cocktails.
“With high-risk patients in mind, we are very concerned about the Omicron subvariant BQ.1.1 being resistant to all approved antibody therapies. Particularly in regions where BQ.1.1 is widespread, physicians should not rely on antibody therapies alone when treating infected high-risk patients, but should also consider administering other drugs such as paxlovid or molnupiravir,” comments study leader Markus Hoffmann on the results of the study.
The finding that the Omicron subvariant BQ.1.1 is already resistant to a new antibody therapy that is about to be approved in the U.S. highlights the importance of developing new antibody therapies against COVID-19.
“The ever-increasing development of antibody resistance of SARS-CoV-2 variants calls for the development of new antibody therapies that are specifically targeted to currently circulating and future viral variants. Ideally, they should target regions in the spike protein that have little potential for escape mutations,” concludes Stefan Pöhlmann, head of the Infection Biology Unit at the German Primate Center – Leibniz Institute for Primate Research.
Reference: “Omicron sublineage BQ.1.1 resistance to monoclonal antibodies” by Prerna Arora, Amy Kempf, Inga Nehlmeier, Sebastian R Schulz, Hans-Martin Jäck, Stefan Pöhlmann and Markus Hoffmann, 18 November 2022,
J&J and Merck Ebola vaccines produce lasting antibodies in children and adults
Ebola vaccines developed by Johnson & Johnson and Merck & Co produced virus-fighting antibodies and appear to be safe in children and adults, according to data from two studies published on Wednesday.
Both companies’ vaccines produced antibodies 14 days after the first of two shots and were detectable at varying levels in both children and adults for one year, data from the studies conducted in Western Africa showed.
The vaccines are designed to target the Zaire strain of the virus, not the Sudan strain of Ebola that recently caused an outbreak and at least 56 deaths in Uganda.
The company logo for Johnson & Johnson is displayed to celebrate the 75th anniversary of the company’s listing at the New York Stock Exchange (NYSE) in New York, U.S., September 17, 2019. REUTERS/Brendan McDermid (Reuters Photos)
One regimen tested a dose of J&J’s vaccine, followed by a booster shot of a vaccine from Danish drugmaker Bavarian Nordic, while another tested two doses of Merck’s vaccine with eight weeks in between. A third option followed the first Merck dose with a placebo.
MODERNA AND MERCK TEAM-UP TO FIGHT MELANOMA
| Ticker | Security | Last | Change | Change % |
|---|---|---|---|---|
| JNJ | JOHNSON & JOHNSON | 179.79 | +0.35 | +0.20% |
| MRK | MERCK & CO. INC. | 111.55 | +1.37 | +1.24% |
“I think the study shows that both the vaccines elicit good antibody responses,” said Dr. H. Clifford Lane, one of the researchers and a clinical director at the U.S. National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH).
Only Merck’s shot can potentially be given as a single dose while J&J’s vaccine may need to continue as a two-dose regimen, Lane added.
FILE- This May 1, 2018, file photo shows Merck corporate headquarters in Kenilworth, N.J. Shares of Merck and Moderna jumped early Tuesday, Dec. 13, 2022, after the drugmakers said a potential skin cancer vaccine they are developing using the same te (AP Photo/Seth Wenig, File / AP Newsroom)
The NIH researchers noted that they were unable to assess the actual level of protection against the disease from the vaccines as no participants contracted Ebola during the trial, which began enrollment in 2017. But they said the vaccines were found to be safe for children and adults.
GSK VACCINE FOR OLDER ADULTS GRANTED FDA PRIORITY REVIEW
“Long-term follow up of the participants in this trial is taking place to determine if and when booster doses might be needed,” said Brian Greenwood, a study co-author from the London School of Hygiene & Tropical Medicine.
A total of 1,400 adults and 1,401 children aged 1 to 17 years old participated in the trials conducted in collaboration with Liberia Ministry of Health and with the University Clinical Research Center and the Center for Vaccine Development-Mali.
The results were published in The New England Journal of Medicine.
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Merck’s vaccine Ervebo was approved by the European regulator and prequalified by the World Health Organization in 2019. J&J’s Zabdeno got European and WHO clearances in 2020 and 2021, respectively. Bavarian Nordic’s Mvabea, used in the J&J regimen, also received European approval in 2020 and WHO prequalification in 2021.
| Ticker | Security | Last | Change | Change % |
|---|---|---|---|---|
| BVNRY | BAVARIAN NORDIC | 10.43 | +0.00 | +0.00% |
J&J and Merck Ebola vaccines produce lasting antibodies in children and adults
Ebola vaccines developed by Johnson & Johnson and Merck & Co produced virus-fighting antibodies and appear to be safe in children and adults, according to data from two studies published on Wednesday.
Both companies’ vaccines produced antibodies 14 days after the first of two shots and were detectable at varying levels in both children and adults for one year, data from the studies conducted in Western Africa showed.
The vaccines are designed to target the Zaire strain of the virus, not the Sudan strain of Ebola that recently caused an outbreak and at least 56 deaths in Uganda.
The company logo for Johnson & Johnson is displayed to celebrate the 75th anniversary of the company’s listing at the New York Stock Exchange (NYSE) in New York, U.S., September 17, 2019. REUTERS/Brendan McDermid (Reuters Photos)
One regimen tested a dose of J&J’s vaccine, followed by a booster shot of a vaccine from Danish drugmaker Bavarian Nordic, while another tested two doses of Merck’s vaccine with eight weeks in between. A third option followed the first Merck dose with a placebo.
MODERNA AND MERCK TEAM-UP TO FIGHT MELANOMA
| Ticker | Security | Last | Change | Change % |
|---|---|---|---|---|
| JNJ | JOHNSON & JOHNSON | 179.79 | +0.35 | +0.20% |
| MRK | MERCK & CO. INC. | 111.55 | +1.37 | +1.24% |
“I think the study shows that both the vaccines elicit good antibody responses,” said Dr. H. Clifford Lane, one of the researchers and a clinical director at the U.S. National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH).
Only Merck’s shot can potentially be given as a single dose while J&J’s vaccine may need to continue as a two-dose regimen, Lane added.
FILE- This May 1, 2018, file photo shows Merck corporate headquarters in Kenilworth, N.J. Shares of Merck and Moderna jumped early Tuesday, Dec. 13, 2022, after the drugmakers said a potential skin cancer vaccine they are developing using the same te (AP Photo/Seth Wenig, File / AP Newsroom)
The NIH researchers noted that they were unable to assess the actual level of protection against the disease from the vaccines as no participants contracted Ebola during the trial, which began enrollment in 2017. But they said the vaccines were found to be safe for children and adults.
GSK VACCINE FOR OLDER ADULTS GRANTED FDA PRIORITY REVIEW
“Long-term follow up of the participants in this trial is taking place to determine if and when booster doses might be needed,” said Brian Greenwood, a study co-author from the London School of Hygiene & Tropical Medicine.
A total of 1,400 adults and 1,401 children aged 1 to 17 years old participated in the trials conducted in collaboration with Liberia Ministry of Health and with the University Clinical Research Center and the Center for Vaccine Development-Mali.
The results were published in The New England Journal of Medicine.
CLICK HERE TO GET THE FOX BUSINESS APP
Merck’s vaccine Ervebo was approved by the European regulator and prequalified by the World Health Organization in 2019. J&J’s Zabdeno got European and WHO clearances in 2020 and 2021, respectively. Bavarian Nordic’s Mvabea, used in the J&J regimen, also received European approval in 2020 and WHO prequalification in 2021.
| Ticker | Security | Last | Change | Change % |
|---|---|---|---|---|
| BVNRY | BAVARIAN NORDIC | 10.43 | +0.00 | +0.00% |