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Researchers Identify Antibodies that May Make Coronavirus Vaccines Unnecessary

A scientific breakthrough by Tel Aviv University: A team of researchers from the university has demonstrated that antibodies isolated from the immune system of recovered COVID-19 patients are effective in neutralizing all known strains of the virus, including the Delta and the Omicron variants. According to the researchers, this discovery may eliminate the need for repeated booster vaccinations and strengthen the immune system of populations at risk.

The research was led by Dr. Natalia Freund and doctoral students Michael Mor and Ruofan Lee of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine. The study was conducted in collaboration with Dr. Ben Croker of the University of California San Diego. Prof. Ye Xiang of Tsinghua University in Beijing. Prof. Meital Gal-Tanamy and Dr. Moshe Dessau of Bar-Ilan University also took part in the study. The study was published in the Nature journal Communications Biology.

The present study is a continuation of a preliminary study conducted in October 2020, at the height of the COVID-19 crisis. At that time, Dr. Freund and her colleagues sequenced all the B immune system cells from the blood of people who had recovered from the original COVID strain in Israel, and isolated nine antibodies that the patients produced. The researchers now found that some of these antibodies are very effective in neutralizing the new coronavirus variants, Delta and Omicron.

Dr. Freund: “In the previous study, we showed that the various antibodies that are formed in response to infection with the original virus are directed against different sites of the virus. The most effective antibodies were those that bound to the virus’s ‘spike’ protein, in the same place where the spike binds the cellular receptor ACE2. Of course, we were not the only ones to isolate these antibodies, and the global health system made extensive use of them until the arrival of the different variants of the coronavirus, which in fact rendered most of those antibodies useless.

“In the current study, we proved that two other antibodies, TAU-1109 and TAU-2310, which bind the viral spike protein in a different area from the region where most of the antibodies were concentrated until now (and were therefore less effective in neutralizing the original strain) are actually very effective in neutralizing the Delta and Omicron variants. According to our findings, the effectiveness of the first antibody, TAU-1109, in neutralizing the Omicron strain is 92%, and in neutralizing the Delta strain, 90%. The second antibody, TAU-2310, neutralizes the Omicron variant with an efficacy of 84%, and the Delta variant with an efficacy of 97%.”

According to Dr. Freund, the surprising effectiveness of these antibodies might be related to the evolution of the virus: “The infectivity of the virus increased with each variant because each time, it changed the amino acid sequence of the part of the spike protein that binds to the ACE2 receptor, thereby increasing its infectivity and at the same time evading the natural antibodies that were created following vaccinations. In contrast, the antibodies TAU-1109 and TAU-2310 don’t bind to the ACE2 receptor binding site, but to another region of the spike protein — an area of the viral spike that for some reason does not undergo many mutations — and they are therefore effective in neutralizing more viral variants. These findings emerged as we tested all the known COVID strains to date.”

The two antibodies, cloned in Dr. Freund’s laboratory at Tel Aviv University, were sent for tests to check their effectiveness against live viruses in laboratory cultures at the University of California San Diego, and against pseudoviruses in the laboratories of the Faculty of Medicine of Bar-Ilan University in the Galilee; the results were identical and equally encouraging in both tests.

Dr. Freund believes that the antibodies can bring about a real revolution in the fight against COVID-19: “We need to look at the COVID-19 pandemic in the context of previous disease outbreaks that humankind has witnessed. People who were vaccinated against smallpox at birth and who today are 50 years old still have antibodies, so they are probably protected, at least partially, from the monkeypox virus that we have recently been hearing about. Unfortunately, this is not the case with the coronavirus. For reasons we still don’t yet fully understand, the level of antibodies against COVID-19 declines significantly after three months, which is why we see people getting infected again and again, even after being vaccinated three times. In our view, targeted treatment with antibodies and their delivery to the body in high concentrations can serve as an effective substitute for repeated boosters, especially for at-risk populations and those with weakened immune systems. COVID-19 infection can cause serious illness, and we know that providing antibodies in the first days following infection can stop the spread of the virus. It is therefore possible that by using effective antibody treatment, we will not have to provide booster doses to the entire population every time there is a new variant.”


Source: Science Daily

Researchers Develop Rapid Test to Keep Track of Immunity to Sars-COV-2 Variants

Jovana Drinjakovic wrote . . . . . . . . .

The experts agree — the pandemic is not over. Infections are ticking up again, fueled by the new variants our immune systems are ill prepared for.

That’s according to a U of T study which found that the antibodies generated in people who were vaccinated and/or recovered from COVID-19 prior to 2022 failed to neutralize the variants circulating today.

The study was led by Igor Stagljar, a professor of biochemistry and molecular genetics, at the Donnelly Centre for Cellular and Biomolecular Research, at Temerty Faculty of Medicine, and Shawn Owen, an associate professor of pharmaceutics and pharmaceutical chemistry, at the University of Utah.

The journal Nature Communications published their findings.

The researchers expect that the antibody test they developed to measure immunity in the study’s participants will become a valuable tool for deciding who needs a booster and when, which will help save lives and avoid future lockdowns.

“The truth is we don’t yet know how frequent our shots should be to prevent infection,” said Stagljar. “To answer these questions, we need rapid, inexpensive and quantitative tests that specifically measure Sars-CoV-2 neutralizing antibodies, which are the ones that prevent infection.”

Many antibody tests have been developed over the past two years. But only a few of the authorized ones are designed to monitor neutralizing antibodies, which coat the viral spike protein so that it can no longer bind its receptor and enter cells.

It’s an important distinction, as only a fraction of all Sars-CoV-2 antibodies generated during infection are neutralizing. And while most vaccines were specifically designed to produce neutralizing antibodies, it’s not clear how much protection they give against variants.

“Our method, which we named Neu-SATiN, is as accurate as, but faster and cheaper than, the gold standard, and it can be quickly adapted for new variants as they emerge,” he said.

Neu-SATiN stands for Neutralization Serological Assay based on split Tri-part Nanoluciferase, and it is a newer version of SATiN, which monitors the complete IgG pool, which they developed last year.

The development of Neu-SATiN was spearheaded by Zhong Yao, a senior research associate in Stagljar’s lab, and Sun Jin Kim, a postdoctoral fellow in Owen’s lab, who are the co-first authors on the paper.

The pin prick test is powered by the fluorescent luciferase protein from a deep-water shrimp. It measures the ability of the viral spike protein to bind the human ACE2 receptor, each of which is attached to a luciferase fragment. The binding brings the luciferase pieces into proximity so that they reconstitute a full-length protein, which gives off a glow of light that is captured by the luminometer instrument. When patient blood sample is added into the mixture, the neutralizing antibodies will bind the spike protein, preventing it from contacting ACE2. Consequently, luciferase remains in pieces, with an accompanying drop in light signal. The plug and play method can be adapted to different variants within a couple of weeks by engineering variant mutations into the spike protein.

The researchers applied Neu-SATiN to blood samples collected from 63 patients with different histories of COVID-19 infection and vaccination up to November 2021. Patient neutralizing capacity was assessed against the original Wuhan strain and the variants, Alpha, Beta, Gamma, Delta and Omicron.

“We thought it would be important to monitor people that have been vaccinated to see if they still have protection and how long it lasts,” said Owen, who did his postdoctoral training in the Donnelly Centre with distinguished bioengineer and University Professor Molly Shoichet. “But we also wanted to see if you were vaccinated against one variant, does it protect you against another variant?”

The neutralizing antibodies were found to last about three to four months when their levels would drop by about 70 per cent irrespective of infection or vaccination status. Hybrid immunity, acquired through both infection and vaccination, produced higher antibody levels at first, but these too dropped significantly four months later.

Most worryingly, infection and/or vaccination provided good protection against the previous variants, but not Omicron, or its sub-variants, BA.4 and BA.5.

The data match those from a recent UK study, which showed that both neutralizing antibodies and cellular immunity, a type of immunity provided by memory T cells, from either infection, vaccination, or both, offered no protection from catching Omicron. In a surprising twist, the UK group also found that infections with Omicron boosted immunity against earlier strains, but not against Omicron itself, for reasons that remain unclear.

It’s important to stress that vaccines still confer significant protection from severe disease and death, said Stagljar. Still, he added that the findings from his team and others call for vigilance in the coming period given that the more transmissible BA4 and BA5 sub-variants can escape immunity acquired from earlier infections with Omicron, as attested by rising reinfections.

“There will be new variants in the near future for sure,” Stagljar said. “Monitoring and boosting immunity with respect to circulating variants will become increasingly important and our method could play a key role in this since it is fast, accurate, quantitative and cheap.”


Source: University of Toronto

A Glucose Meter Could Soon Say Whether You Have SARS-CoV-2 Antibodies

Over-the-counter COVID tests can quickly show whether you are infected with SARS-CoV-2. But if you have a positive result, there’s no equivalent at-home test to assess how long you’re protected against reinfection. In the Journal of the American Chemical Society, researchers now report a simple, accurate glucose-meter-based test incorporating a novel fusion protein. The researchers say that consumers could someday use this assay to monitor their own SARS-CoV-2 antibody levels.

Vaccines against SARS-CoV-2 and infection with the virus itself can guard against future infections for a while, but it’s unclear exactly how long that protection lasts. A good indication of immune protection is a person’s level of SARS-CoV-2 antibodies, but the gold standard measurement – the enzyme-linked immunosorbent assay (ELISA) – requires expensive equipment and specialized technicians.

Enter glucose meters, which are readily available, easy to use and can be integrated with remote clinical services. Researchers have been adapting these devices to sense other target molecules, coupling detection with glucose production. For example, if a detection antibody in the test binds to an antibody in a patient’s blood, then a reaction occurs that produces glucose — something the device detects very well. Invertase is an attractive enzyme for this type of analysis because it converts sucrose into glucose, but it’s difficult to attach the enzyme to detection antibodies with chemical approaches. So, Netzahualcóyotl Arroyo-Currás, Jamie B. Spangler and colleagues wanted to see whether producing a fusion protein consisting of both invertase and a detection antibody would work in an assay that would allow SARS-CoV-2 antibody levels to be read with a glucose meter.

The researchers designed and produced a novel fusion protein containing both invertase and a mouse antibody that binds to human immunoglobulin (IgG) antibodies. They showed that the fusion protein bound to human IgGs and successfully produced glucose from sucrose. Next, the team made test strips with the SARS-CoV-2 spike protein on them. When dipped in COVID-19 patient samples, the patients’ SARS-CoV-2 antibodies bound to the spike protein. Adding the invertase/IgG fusion protein, then sucrose, led to the production of glucose, which could be detected by a glucose meter. They validated the test by performing the analysis with glucose meters on a variety of patient samples, and found that the new assay worked as well as four different ELISAs. The researchers say that the method can also be adapted to test for SARS-CoV-2 variants and other infectious diseases.


Source: American Chemical Society

Chinese Researchers Claim to Have Discovered a ‘Godsend’ Antibody that Can Defeat Omicron

Chinese scientists believe they have discovered a powerful new synthetic antibody that can combat SARS-CoV-2, the virus that causes COVID-19.

The news comes as the US Food and Drug Administration, which regulates drug production, is cutting production of older antibody drugs that have a minimal or no impact on the variant.

Upon emergence in November 2021, the Omicron variant created untold problems for health professionals around the world. It seems to have evaded every defence used to control the spread of previous strains of the virus, including masks, vaccines, and antibody treatments.

Researchers at Fudan University in Shanghai, however, think they may have discovered a recipe for a synthetic antibody that would prove to be a match for Omicron.

Researchers made the discovery while investigating another disease.

According to the lead scientist, Professor Huang Jinghe of Fudan University in Shanghai, the discovery put humans “a step ahead in the race” against the pandemic.

An article describing their work was published on the bioRxiv preprint website. It is yet to be peer reviewed and is titled “Combating the SARS-CoV-2 Omicron variant with non-Omicron neutralizing antibodies.”

In an interview with the South China Morning Post, Professor Huang Jinghe, an instructor at Fudan University and the lead scientist in the study, said she accidentally synthesized the antibody out of two different natural antibodies produced by human immune cells in response to encountering SARS-CoV-2.

In their individual forms, both natural antibodies had little chance of stopping Omicron, but in a new form, the man-made antibody was able to breach the virus’ defences by using a string of moves Huang likened to that in video games like “Street Fighter.”

Omicron can only be neutralized by a handful of antibodies on the planet, said Jighe adding that she feels like she has been hit by God’s grace.

The researcher called the discovery “a godsend” and said it would put humans “a step ahead” in the race against the ultra-transmissible virus.

Huang explained that she wasn’t trying to develop an anti-Omicron antibody, but had been researching another infectious disease, but upon discovering the antibody’s efficacy, decided to test it out on Omicron as well.

The authors report that their antibody is effective against other versions of SARS-CoV-2, as well as against SARS-CoV-1, a related disease better known as Severe Acute Respiratory Syndrome (SARS). Theoretically, it will also work against future variants.


Source : WION

COVID-19 Can Trigger Self-Attacking Antibodies

Infection with the virus that causes COVID-19 can trigger an immune response that lasts well beyond the initial infection and recovery—even among people who had mild symptoms or no symptoms at all, according to Cedars-Sinai investigators. The findings are published in the Journal of Translational Medicine.

When people are infected with a virus or other pathogen, their bodies unleash proteins called antibodies that detect foreign substances and keep them from invading cells. In some cases, however, people produce autoantibodies that can attack the body’s own organs and tissues over time.

The Cedars-Sinai investigators found that people with prior infection with SARS-CoV-2, the virus that causes COVID-19, have a wide variety of autoantibodies up to six months after they have fully recovered. Prior to this study, researchers knew that severe cases of COVID-19 can stress the immune system so much that autoantibodies are produced. This study is the first to report not only the presence of elevated autoantibodies after mild or asymptomatic infection, but their persistence over time.

“These findings help to explain what makes COVID-19 an especially unique disease,” said Justyna Fert-Bober, PhD, research scientist in the Department of Cardiology at the Smidt Heart Institute and co-senior author of the study. “These patterns of immune dysregulation could be underlying the different types of persistent symptoms we see in people who go on to develop the condition now referred to as long COVID-19.”

To conduct their study, the Cedars-Sinai research team recruited 177 people with confirmed evidence of a previous infection with SARS-CoV-2. They compared blood samples from these individuals with samples taken from healthy people prior to the pandemic. All those with confirmed SARS-CoV-2 infection had elevated levels of autoantibodies. Some of the autoantibodies also have been found in people with diseases in which the immune system attacks its own healthy cells, such as lupus and rheumatoid arthritis.

“We found signals of autoantibody activity that are usually linked to chronic inflammation and injury involving specific organ systems and tissues such as the joints, skin and nervous system,” said Susan Cheng, MD, MPH, MMSc, director of the Institute for Research on Healthy Aging in the Department of Cardiology at the Smidt Heart Institute and co-senior author of the study.

Some of the autoantibodies have been linked to autoimmune diseases that typically affect women more often than men. In this study, however, men had a higher number of elevated autoantibodies than women.

“On the one hand, this finding is paradoxical given that autoimmune conditions are usually more common in females,” Fert-Bober said. “On the other hand, it is also somewhat expected given all that we know about males being more vulnerable to the most severe forms of COVID-19.”

The research team is interested in expanding the study to look for the types of autoantibodies that may be present and persist in people with long-haul COVID-19 symptoms. Because this study was in people infected before the advent of vaccines, the researchers will also examine whether autoantibodies are similarly generated in people with breakthrough infections.

“If we can better understand these autoantibody responses, and how it is that SARS-CoV-2 infection triggers and drives these variable responses, then we can get one step closer to identifying ways to treat and even prevent these effects from developing in people at risk,” Cheng said.


Source: Cedars Sinai

Finland Study: Antibodies Present More than One Year after COVID-19 Infection

The majority of those infected with the coronavirus had neutralizing antibodies after more than a year, according to a study by the National Institute for Health and Welfare published preprint in MedRxiv. A recent study looked at the persistence of antibodies produced by a diseased coronavirus disease six months and a year after infection.

As many as 97% of subjects had IgG antibodies recognizing the coronavirus peak protein one year after infection. Although antibodies were detected in many, their levels after one year were about one-third lower than they had been six months after infection.

“Investigating antibody levels after coronavirus disease provides important information that also helps assess the protection and duration of vaccines,” says Merit Melin , THL’s research manager.

The subjects had been diagnosed with a coronavirus infection in the spring of 2020. The infection had been confirmed by a PCR test, after which they had not been diagnosed with a new coronavirus infection and had not received a coronavirus vaccine prior to sampling.

A total of 1292 individuals were tested for antibodies six months after infection and 367 individuals one year later. Fifteen percent of those surveyed after six months and 13 percent of those surveyed after one year had had a serious coronavirus infection requiring hospitalization.

Patients with severe disease requiring hospitalization had significantly higher levels of antibodies than those with mild disease. All patients with severe disease still had neutralizing antibodies after one year.

“The results of the study show that after coronavirus infection, neutralizing antibodies and protection against a new infection are maintained for a long time if the amount of antibodies was initially high,” says Melin.

The study also looked at the ability of the antibodies to neutralize altered viral forms. The amount of neutralizing antibodies against the Alpha variant was slightly lower compared to the virus strain and significantly lower against the Beta and Delta variants. Especially in patients with mild disease, the level of antibodies against viral variants was reduced.

Infections caused by viral variants have also been reported in vaccinees after both single and double vaccine doses. However, vaccines provide good protection against a serious form of the disease caused by viral variants.

“The protection against serious disease that results from infection or vaccination is based not only on antibodies but also on cell-mediated immunity and memory cells that activate and produce antibodies when they encounter a pathogen,” Melin explains.


Source : Outbreak News Today


Read more at Wiley

Persistence of neutralizing antibodies a year after SARS-CoV-2 infection in humans (pdf) . . . . .

Detecting COVID-19 Antibodies in 10-12 Seconds

Researchers at Carnegie Mellon University report findings on an advanced nanomaterial-based biosensing platform that detects, within seconds, antibodies specific to SARS-CoV-2, the virus responsible for the COVID-19 pandemic. In addition to testing, the platform will help to quantify patient immunological response to the new vaccines with precision.

The results were published this week in the journal Advanced Materials. Carnegie Mellon’s collaborators included the University of Pittsburgh (Pitt) and the UPMC.

The testing platform identifies the presence of two of the virus’ antibodies, spike S1 protein and receptor binding domain (RBD), in a very small drop of blood (about 5 microliters). Antibody concentrations can be extremely low and still detected below one picomolar (0.15 nanograms per milliliter). This detection happens through an electrochemical reaction within a handheld microfluidic device which sends results almost immediately to a simple interface on a smart phone.

“We utilized the latest advances in materials and manufacturing such as nanoparticle 3D printing to create a device that rapidly detects COVID-19 antibodies,” said Rahul Panat, an associate professor of mechanical engineering at Carnegie Mellon who uses specialized additive manufacturing techniques for research ranging from brain-computer interfaces to biomonitoring devices.

An additive manufacturing technology called aerosol jet 3D printing is responsible for the efficiency and accuracy of the testing platform. Tiny, inexpensive gold micropillar electrodes are printed at nanoscale using aerosol droplets that are thermally sintered together. This causes a rough, irregular surface that provides increased surface area of the micropillars and an enhanced electrochemical reaction, where antibodies can latch on to antigens coated on the electrode. The specific geometry allows the micropillars to load more proteins for detection, resulting in very accurate, quick results.

The test has a very low error rate because the binding reaction between the antibody and antigen used in the device is highly selective. The researchers were able to exploit this natural design to their advantage.

The results come at an urgent time during the COVID-19 pandemic. “Because our technique can quantify the immune response to vaccination, it is very relevant in the current environment,” Panat said.

Panat collaborated with Shou-Jiang Gao, leader of the cancer virology program at UPMC’s Hillman Cancer Center and professor of microbiology and molecular genetics at Pitt. Azahar Ali, a researcher in Panat’s Advanced Manufacturing and Materials Lab, was the lead author of the study.

Rapid diagnosis for the treatment and prevention of communicable diseases is a public health issue that goes beyond the current COVID-19 pandemic. Because the proposed sensing platform is generic, it can be used for the rapid detection of biomarkers for other infectious agents such as Ebola, HIV, and Zika. Such a quick and effective test could be a game-changer for controlling the spread of diseases.


Source: EurekAlert!