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Breakthrough Antibody Discovery Could Mean End to Covid Vaccines

AHA Publisher — Mon, 12 Sep 2022 07:00:55 +0000

Nicky Blackburn via Israel21c – A team of researchers has discovered 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 Omicron variants. According to the researchers, targeted treatment with these antibodies delivered to the body in high concentrations may eliminate the need for repeated booster vaccinations and strengthen the immune system of populations at risk. The research, which was carried out at Tel Aviv University, is the continuation of a previous study conducted in October 2020. Led by Dr. Natalia Freund, from the university’s Clinical Microbiology and Immunology Department, in the initial study the research team 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. In the new study, the researchers found that some of these antibodies are very effective in neutralizing the new coronavirus variants, Delta and Omicron. “In the current study, we proved that two 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,” said Freund. “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%.” Freund believes that the efficacy of these antibodies might be related to the evolution of the virus, which became increasingly infectious with each variant, changing the amino acid sequence of the part of the spike protein that binds to the ACE2 receptor. “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 are therefore effective in neutralizing more viral variants,” she said. “These findings emerged as we tested all the known COVID strains to date,” she added. The two antibodies cloned in Freund’s laboratory, were sent for tests to check 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. Freund said that she believes these antibodies can bring about a real revolution in the fight against COVID-19, by providing a viable alternative to booster doses. “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,” she explained. “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,” she said. “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,” she concluded. The research was also carried out by doctoral students Michael Mor and Ruofan Lee of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine, and 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. The study was published in the Nature journal Communications Biology. To read the original article click here.

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Researchers Discover New, Potent COVID-19 Antibody Cocktail

AHA Publisher — Wed, 23 Mar 2022 07:00:34 +0000

Texas Biomedical Research Institute via Newswise – SAN ANTONIO (March 18, 2022) – As SARS-CoV-2 has continued to evolve and outsmart existing treatments, scientists have not let up looking for ever-more effective tools to keep people safe and successfully recover from COVID-19, and to prepare for future outbreaks. A long-time partnership between Texas Biomedical Research Institute Professor Luis Martinez-Sobrido and University of Alabama at Birmingham Associate Professor James Kobie has resulted in the discovery of a promising treatment – one that the virus cannot so easily escape. The collaborators found two antibodies that target different parts of the virus’s spike protein and more importantly, block different steps required for viral infection. “This cocktail has worked against all SARS-CoV-2 variants, including Omicron, as well as SARS-CoV and MERS-CoV – the two coronaviruses that caused past outbreaks,” says Martinez-Sobrido. “Given that, we expect this antibody cocktail to also work against future coronavirus outbreaks as well.” The researchers recently shared a pre-print of their research paper describing the cocktail. The first antibodytargets the top of the spike protein, which helps block the virus from entering a person’s cells. It is similar to other antibody treatments, but continues to work against the latest variants, while others have not. The second antibody targets a lower section of the spike protein, which helps block the virus from fusing with the cell’s membrane and releasing its genetic material into the cell. This second antibody has the potential to be a game changer because it is targeting a much more stable section of coronaviruses that has been conserved, or remains the same, in SARS-CoV and MERS-CoV through all the variants of SARS-CoV-2, including Omicron. SARS-CoV-2 has continued to evolve throughout the pandemic, as is typical and expected of any virus. Some of those mutations have meant other antibodies can no longer latch on and neutralize the virus. But if SARS-CoV-2 mutates this stable lower section of the spike’s stem, it will not be able to replicate inside its host, and would die out. “It is the Achilles’ heel of the virus,” says Tracey Baas, Innovations Manager at Texas Biomed and manager for the Vaccine Development Center of San Antonio. The antibodies were found in the serum of recovered COVID-19 patients. The UAB team collected blood samples for research with patients’ informed consent, and screened them for SARS-CoV-2-specific antibodies. The UAB team then replicated the antibodies in large enough quantities so they could be used in multiple studies. Those antibodies were sent to Texas Biomed, where researchers tested them against the virus in biosafety laboratories, first in cells and then in small animal models, which were established or validated at Texas Biomed. The team was able to see the results in cells and animal models in real time using fluorescent viruses they developed. “We have tested hundreds and hundreds of antibodies since the start of the pandemic,” Martinez-Sobrido says. “But all that effort paid off by identifying these two novel antibodies that target different parts of the spike protein, making for an extremely effective, broad-spectrum treatment.” UAB and Texas Biomed teamed up with Aridis Pharmaceuticals to develop successful antibody candidates into an inhaled treatment, much like inhalers for asthma. This delivery system promises to be low cost and easy to distribute because it can be self-administered. “Our researchers used their decades of experience to step back and look for solutions to tough problems,” says Cory Hallam, VP of Business Development at Texas Biomed. “But we are not in the business of manufacturing treatments; we partner with industry to quickly translate discoveries made in our labs into approved products to treat people.” Texas Biomed is actively working with Aridis to identify potential manufacturing partners that can produce the treatments, so they can move into human clinical trials. The antibodies have many promising applications, by treating those who fall ill around the world, and by providing antibodies to people who have trouble creating their own even though they have been vaccinated. “Right now, we don’t have a sterilizing vaccine for COVID-19 like we do for polio, so these antibodies help complete the package of prevention and treatment,” Hallam says. The Bill and Melinda Gates Foundation recently awarded Aridis, in collaboration with Texas Biomed and UAB, nearly $2 million to develop low cost, inhaled antibody treatments for COVID-19, the flu and other infectious pathogens. Some of that funding will support continued research, development and testing at Texas Biomed, including studies to ensure the cocktail remains effective as new variants emerge. To read the original article click here.

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Antibodies Perform Best After Covid Infection, Not Vaccine

AHA Publisher — Fri, 11 Feb 2022 08:00:07 +0000

Abigail Klein Leichman via Israel21c – Over time, the number of SARS-CoV-2 antibodies falls in both previously infected and vaccinated people, but the performance of antibodies improves only after previous infection and not vaccination. This groundbreaking research, led by Dr. Carmit Cohen of Israel’s Sheba Medical Center, will be presented at the European Congress of Clinical Microbiology and Infectious Diseases in April. Cohen’s finding may explain why previously infected patients appear to be better protected against a new Covid infection than those who have only been vaccinated. She and her colleagues analyzed antibody-induced immune response in 130 recovered individuals for up to a year and compared it to 402 matched individuals who were double-vaccinated with the Pfizer vaccine but never had Covid-19. The researchers found that the numbers of antibodies a month after vaccination were higher than those in the Covid-19 recovered patients. However, these numbers declined more steeply in the vaccinated group. While the avidity (antibody performance quality) index was higher in vaccinated individuals than in recovered patients initially, avidity did not significantly change over time in vaccinated individuals but increased gradually in recovered patients. This could explain why double-vaccinated individuals who never contracted Covid-19 are more likely to experience infection after six months. The study also found that, contrary to expectations, antibodies of recovered patients with a body mass index of 30 or higher (in the obese range) were higher at all time points when compared with those with a BMI under 30 (overweight to normal weight range). The obese people who had been previously infected were therefore better protected against future infection. Of all recovered patients, 42 (36%) experienced long Covid including mental health (5%), neurological (9%), cardiovascular (5%) and respiratory (31%) symptoms. The authors conclude: “While the number of antibodies decrease with time in both Covid-19 recovered patients and vaccinated individuals, the quality of antibodies increases following infection but not after vaccination. These results provide specific characteristics of the immune response that may explain the differential protection against Covid-19 in previously infected and vaccinated individuals.” To read the original article click here.

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New Study Validates Benefits of Convalescent Plasma for Some COVID-19 Patients

AHA Publisher — Wed, 26 Jan 2022 08:00:26 +0000

NYU Langone Health via Newswise – Transfusions of blood plasma donated by people who have already recovered from infection with the pandemic virus may help other patients hospitalized with COVID-19, a new international study shows. The treatment, known as convalescent plasma, is still considered experimental by the U.S. Food and Drug Administration (FDA). Plasma contains antibodies, blood proteins that are part of the immune system. Shaped so they can attach to the virus that causes COVID-19, SARS-CoV-2, antibodies glom onto and tag it for removal from the body, researchers say. Led by researchers at NYU Grossman School of Medicine, the study showed that among 2,341 men and women, those who received an injection of convalescent plasma soon after hospitalization were 15% less likely to die within a month from COVID-19 than those who did not receive convalescent plasma or those who received an inactive saline placebo. Notably, the researchers found that the biggest benefits for the therapy were among patients most at risk for severe complications because of pre-existing conditions, such as diabetes or heart disease. The treatment, which contains antibodies and other immune cells needed to fight the infection, also appears to benefit those with type A or AB blood. “Our results show that, overall, patients hospitalized with COVID-19 may derive modest benefit from convalescent plasma, with some patient subgroups benefiting more than others,” says study lead investigator and biostatistician Andrea Troxel, ScD. With respect to the groups most likely to benefit, the FDA on Dec. 28, 2021, revised the Emergency Use Authorization for convalescent plasma, limiting its use to patients with diseases that suppress their immune systems, or that receive medical treatments with the same effect. “Patients with co-existing disease were most likely to show improvement from convalescent plasma, probably because they have the most difficulty producing antibodies to fight their infection,” adds Troxel. “The infused plasma boosts their body’s ability to fight the virus, but only in the early stage of the disease and before the illness overwhelms their body.” The current study findings, published in the journal JAMA Network Open online Jan. 25, come from the pooling of patient information from eight recently completed studies in the United States, Belgium, Brazil, India, the Netherlands, and Spain on the effects of convalescent plasma for COVID-19. These benefits of the treatment are only likely to become clear as more data from the trials become available, says Troxel, a professor in the Department of Population Health at NYU Langone. This is because the data from individual trials are too small to show the treatment’s overall impact on subsets of patients, she says. Some individual studies have showed the therapy to be ineffective or of limited value. Study co-investigator Eva Petkova, PhD, says the team is using its study data to create a scoring system of patient descriptors, including age, stage of COVID-19, and co-existing diseases, making it easier for clinicians to calculate who stands to benefit most from use of convalescent plasma. “Our treatment benefit index is designed to serve as a quick and effective tool for physicians to use in deciding when to administer convalescent plasma for COVID-19,” says Petkova, a professor in the Departments of Population Health and Child and Adolescent Psychiatry at NYU Langone. The index is freely available online at [http://covid-convalescentplasma-tbi-calc.org]. For the study, researchers grouped all patient information from smaller, separate clinical investigations about convalescent plasma therapy, including trials at NYU Langone, Albert Einstein College of Medicine and Montefiore Medical Center, Zuckerberg San Francisco General Hospital, and the University of Pennsylvania in Philadelphia. Researchers hoped any benefits or disadvantages in treatment would be easier to spot among the largest possible sample of patients. All trials were randomized and controlled, meaning that the patient had a random chance of being assigned to receive convalescent plasma or not to receive it. Included in the analysis were data from another multicenter U.S. study published separately in December 2021 in JAMA Internal Medicine. That study in 941 patients hospitalized with COVID-19 showed that patients receiving high doses of convalescent plasma therapy and not on other medications, such as remdesivir or corticosteroids, were likely to benefit from the blood plasma treatment. Study co-primary investigator Mila Ortigoza, MD, PhD, an assistant professor in the Departments of Medicine and Microbiology at NYU Langone, says these initial results supported the idea that convalescent plasma could be a feasible treatment option, especially when other therapies are not yet available, as at the beginning of a pandemic. In addition, convalescent plasma collected from previously infected and subsequently vaccinated donors (VaxPlasma) would contain antibodies in high enough quantities and diversity that could provide added protection against emerging viral variants, says Ortigoza. Viruses typically mutate genetically (acquire random changes in their DNA or RNA codes) over the course of any pandemic. For this reason, convalescent plasma has the potential to offer effective treatment more quickly after such mutations than treatment types that tend to become less effective with time and must undergo a re-design process to address a new variant, such as monoclonal antibody treatments. To read the original article click here.

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New Study Reveals Antibodies from Fighting COVID-19 Infection Can Last More Than One Year

AHA Publisher — Thu, 07 Oct 2021 07:00:55 +0000

Steve Warren via CBN News – A new peer-reviewed study has confirmed what several researchers and even some health professionals have been saying all along: Most people infected with the COVID-19 virus retain the antibodies to continue to fight it – often for many months following their initial infection. Just The News reports the European Journal of Immunology accepted a study on Sept. 24 from scientists at the Finnish Institute for Health and Welfare, who studied 1,292 subjects eight months after infection for the presence of antibodies. The researchers found that 96% of their test subjects were still carrying antibodies and 66% still had the nucleoprotein IgG antibody. The Immunoglobulin G (IgG) antibody helps your immune system remember how to fight infections like the COVID-19 virus. But the Finnish scientists’ research went even further. They randomly selected 367 subjects from the original study group who were not vaccinated for a year following their infection. The scientists found that 89% of subjects still had neutralizing antibodies, and 36% with the IgG antibody, according to Just The News. Those subjects who had a severe COVID-19 infection had higher antibody levels, anywhere from two to seven times as many antibodies as those with mild infections at least 13 months after contracting the disease, the study noted. Even though the antibodies provided long-lasting protection against the COVID virus, their ability to fight the Alpha, Beta, and Delta variants diminished over a period of several months. However, the neutralizing antibodies “were only slightly reduced” in the Alpha variant and “considerably declined” in the Beta variant. But “over 80% of the subjects who had recovered from severe” COVID-19 infection still had neutralizing antibodies against the Delta variant a year after being infected, the study pointed out. Natural immunity to the COVID-19 virus has been touted by some health professionals throughout the pandemic. Former FDA Commissioner Scott Gottlieb, M.D. told CBN News in September that in addition to taking the vaccine, another way to achieve immunity is through natural means. “I think we need to recognize that people who have immunity that’s acquired through infection, that immunity is durable, and it appears it is quite robust,” he said. “I think the question from a clinical standpoint is how long it’s going to last.” As CBN News reported in August, a George Mason University (GMU) law professor who sued the school over its COVID-19 vaccine mandate was ultimately granted a medical exemption by the school. Todd Zywicki, the law professor at the Fairfax, Virginia, school said he had COVID-19 and defeated it, therefore his natural immunity, he argued, should prevent him from having to get the vaccination. According to University Business, Zywicki claimed the vaccine mandate enforced by the school was excessive since he already had natural immunity through antibodies he acquired after he successfully recovered from the virus. His attorneys revealed Zywicki took six tests to prove those antibodies were still active in his immune system. Dr. Marty Makary, a professor at Johns Hopkins School of Public Health, told CBN Newsin late June that medical experts got it wrong when they dismissed natural immunity to the virus. “It’s one of the biggest failures of our medical establishment to dismiss natural immunity,” he told CBN News, pointing to two new studies that show its efficacy. “It works. It’s durable. You may not need the vaccine and it’s probably long-lasting. It’s probably life-long.” In a U.S. News & World Report op-ed published later in August, Makary said an Israeli study showed natural immunity is 6.7 times greater than for vaccinated people. To read the original article click here.

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Israeli Scientists Discover How to Reverse Cell Aging

AHA Publisher — Fri, 03 Sep 2021 07:00:53 +0000

Maayan Jaffe-Hoffman via The Jerusalem Post – Scientists from the Technion-Israel Institute of Technology say they have found a way to rejuvenate the aging process of the body’s immune system. Prof. Doron Melamed and doctoral student Reem Dowery sought to understand why the elderly population is more susceptible to severe cases of COVID-19 and why the vaccines seem to be less effective and wane faster among this population. The results of their work were published this month in the peer-reviewed, online medical journal Blood. The secret begins with B cells, also known as B lymphocytes. These are the cells that produce antibodies against any pathogen that enters the body. They play a key role in protecting people from viruses and diseases. B cells are produced in bone marrow and then travel through the blood to lymph nodes and the spleen, where they wait for pathogens to enter and then attack them. “When you are young, you have young cells, and young cells have a very diverse ability to recognize anything [pathogenic] that comes into your body,” Melamed told The Jerusalem Post. B cells do not live long, but they are constantly being replenished by new ones sent from the bone marrow, creating what Melamed calls “homeostasis,” a state in which the total number of B cells in the bone marrow and outside remains constant. However, B cells do not just disappear. They turn into “memory” B cells so that if the body is exposed to a previous pathogen, the individual will not get sick. That is because the immune response will be fast and robust, and it will eliminate the pathogen, often without the individual knowing he or she had been exposed to it. Unlike B cells, memory cells are long-lived. “Imagine you are growing into adulthood, and you become an adult and then an older person,” Melamed said. “You accumulate in your body many memory cells. You are exposed all the time to pathogens, and hence you make more and more memory cells. Because these are so long-lived, there is no room left for new B cells.” What happens when a new pathogen, such as the coronavirus, comes along? There are no young B cells that can recognize it. That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. As noted, this happens because of the body’s need for homeostasis, something that Melamed’s lab discovered a decade ago. BUT THIS year, they took the discovery another step and figured out a mechanism to override the system. “We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.” It also means that, over time, specific drugs or treatments can be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells. What happens when a new pathogen, such as the coronavirus, comes along? There are no young B cells that can recognize it. That is one of the reasons why older people are more susceptible to severe COVID-19 and many other diseases. As noted, this happens because of the body’s need for homeostasis, something that Melamed’s lab discovered a decade ago. BUT THIS year, they took the discovery another step and figured out a mechanism to override the system. “We found specific hormonal signals produced by the old B cells, the memory cells, that inhibit the bone marrow from producing new B cells,” Melamed said. “This is a huge discovery. It is like finding a needle in a haystack.” It also means that, over time, specific drugs or treatments can be found to inhibit one of the hormones in the signaling pathway and get the bone marrow to produce new B cells. To validate their theory, Melamed’s lab collaborated with the departments of hematology and rheumatology at Sourasky Medical Center in Tel Aviv and Rambam Health Care Campus in Haifa. As part of treatment for some medical conditions, such as lupus, lymphoma and multiple sclerosis, patients undergo B cell depletion, meaning a significant amount of memory B cells is removed from their bodies. Examining older patients who underwent this procedure, the group found that their immune systems rejuvenated, and their bodies could produce new B cells again. An effect similar to B cell depletion can be produced by inhibiting one of the hormones in the signaling pathway that suppresses the production of new B cells. “Now we understand that there is some kind of conversation between compartments in the body, between how B cells are produced and what controls that,” Melamed said. In the interim, he recommended that doctors use this knowledge to protect the elderly better, such as by instituting a vaccination program targeted just for the adult population that preempts variants with an additional shot. “Even every three or four months, vaccinate them again and again to ensure they maintain high antibodies,” Melamed said. He also suggested mixing vaccines, such as combining a shot of a Pfizer mRNA vaccine with an AstraZeneca booster given several months later, “which may generate better stimulation of the elderly immune system.” At the same time, clinical trials would be needed to determine how to safely inhibit the hormones to find a longer-term solution, hopefully before the next pandemic, Melamed said. To read the original article click here.

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Scientists Identify Natural SARS-CoV-2 Super Immunity Against 23 Variants

AHA Publisher — Mon, 12 Jul 2021 07:00:52 +0000

Dr. Sanchari Sinha Dutta, Ph.D. via News-Medical – A team of international scientists has recently identified ultrapotent anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies from convalescent donors. The antibodies are capable of neutralizing a wide range of SARS-CoV-2 variants even at sub-nanomolar concentrations. In addition, the combinations of these antibodies reduce the risk of generating escape mutants in vitro. The study is published in the journal Science. Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19), is an enveloped, positive-sense, single-stranded RNA virus belonging to the human beta-coronavirus family. The spike glycoprotein on the viral envelop is composed of two subunits S1 and S2. Of which, the S1 subunit directly binds to the host cell angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) to initiate the viral entry process. The majority of therapeutic antibodies against SARS-CoV-2 have been designed based on the native spike protein sequence found in the original Wuhan strain of SARS-CoV-2. Thus, novel viral variants with multiple spike protein mutations may likely develop resistance against these antibodies. In this context, studies have shown that antibodies developed in response to currently available COVID-19 vaccines have less efficiency in neutralizing novel variants of concern (VOCs) of SARS-CoV, including B.1.1.7, B.1.351, P1, and B.1.617.2. In the current study, the scientists have isolated and characterized anti-spike RBD antibodies from COVID-19 recovered patients. Antibody Identification The antibodies were isolated from four convalescent donors infected with the Washington-1 (WA-1) strain of SARS-CoV-2. The spike sequence in the WA-1 strain is similar to the spike sequence in the original Wuhan strain. The B cells isolated from donor-derived blood samples were sorted for antibody identification. This led to the identification of four potent neutralizing antibodies targeting the spike RBD. These antibodies showed a high affinity for the SARS-CoV-2 spike even at nanomolar concentrations. To determine whether the high potency antibodies could block ACE2 – spike binding, interferometry ACE2-competition and cell surface binding assays were performed. The findings revealed that of 4 antibodies, two bound to RBDs in the “up position” and two bound to RBDs in the “down position.” Moreover, three out of four antibodies directly blocked the RBD – ACE2 interaction, and one indirectly inhibited the interaction through steric hindrance – the slowing of chemical reactions due to steric bulk. Antibody-Mediated Neutralization All experimental antibodies exhibited significantly higher potency in neutralizing D614G mutation-containing variants than the WA-1 strain. Further analysis with lentiviral particles pseudotyped with spike variants indicated that the antibodies maintain high potency in neutralizing a diverse set of 10 spike variants. Importantly, three out of four experimental antibodies showed high efficacy in neutralizing 13 circulating variants of concern/interest of SARS-CoV-2, including B.1.1.7, B.1.351, B.1.427, B.1.429, B.1.526, P.1, P.2, B.1.617.1 and B.1.617.2. Structural and Functional Analysis of Antibodies Cryo-electron microscopic analyses of antibody-antigen complex structures revealed that two antibodies with the highest neutralization potency bind to the spike protein with all RBDs in “up position.” Further structural analyses revealed that the epitope binding modes of the antibodies are responsible for high neutralizing potency against SARS-CoV-2 VOCs. The binding and neutralizing ability of the antibodies was negatively impacted by three spike mutations, including F486R, N487R, and Y489R. Antibody Resistance Antibody selection pressure was applied to the WA-1 strain to identify potential escape mutations that may appear during the viral infection. The positive selection pressure was applied by incubating the virus with increasing concentrations of the antibodies to trigger antibody resistance. In two of the most potent antibodies, one was negatively impacted by a single F486S mutation, and the other one was impacted by the F486L, N487D, and Q493R mutations. However, the Q493R mutation showed a negligible impact on binding and neutralization. Further analysis revealed that these escape mutations are primarily absent in circulating viral variants, indicating the absence of selection pressure. By conducting multiple rounds of selection using combination treatments with two antibodies, it was observed that antibody combinations might reduce the risk of escape mutation acquisition and subsequent development of resistant viral variants. To read the original article click here.

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Study Suggests SARS-CoV-2 Antibodies in Breast Milk Are Robust, Neutralizing and Durable

AHA Publisher — Wed, 31 Mar 2021 07:00:42 +0000

Dr. Liji Thomas, MD via News-Medical – The pandemic of coronavirus disease 2019 (COVID-19) has caused over 123.7 million cases and has claimed more than 2.7 million lives worldwide. However, the infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects children and adolescents with strikingly less severity than adults. Infants are also included in this low-risk group. However, a new preprint on the bioRxiv* server addresses the issue of passive immunity for newborns via breast milk. Importance of the Study Among infants with COVID-19, one in ten require intensive care for severe illness. A significant minority also shows signs of Multisystem Inflammatory Syndrome in Children(MIS-C) associated with COVID-19, setting in after weeks or months. The possibility of transmitting infection also exists with infants, adding reason to protect this group against infection. Breast Milk Antibodies Breast milk contains about 0.6 mg/mL of antibodies in the form of immunoglobulin (IG). About 90% of this is IgA, mostly secretory (sIgA). This comprises a complex of IgA antibodies, the J-chain and secretory component (SC) proteins, forming antibody polymers. The entero-mammary link is in action to produce sIgA from the gut-associated lymphoid tissue (GALT) and from B cells recruited from other mucosal surfaces, as well as from the draining lymphatics of the breast tissue. This form of IgA is very stable and does not easily break down under enzymatic action, whether in the milk or the infant’s gut or in the mucosae of the gut, the upper airway and the lungs. The concentration of IgA in the infant’s stomach drops by half within two hours, while that of IgG drops by three-quarters. Preterm infants fail to show a decrease in IgA concentration within the first three months after birth, which is important given their increased susceptibility to infection. Earlier Research An earlier study by the same authors showed that all milk samples from 15 recently recovered COVID-19 mothers contained significant IgA binding activity against the viral spike protein. About 80% of samples were also observed to contain antibodies specific to the receptor-binding domain (RBD), including secretory antibodies. Only a few showed anti-RBD IgG or IgM activity, indicating that the anti-RBD IgA was secretory in nature. What Were the Results? The current study showed the types of anti-spike antibodies in breast milk from a larger group of donors, collected at 4-6 weeks after infection. The antibody profile in milk was studied using IgA ELISA against the recombinant trimeric spike protein of the virus. The researchers found that 88% of samples were positive for anti-spike IgA and that binding was higher for spike-specific binding compared to controls. Titration of 40 positive samples showed positive IgA endpoint titers in 95% of them (indicating the highest dilution at which the reaction is positive). Of these, half showed a titer five-fold or more the endpoint titer of the positive cutoff value, entitling them to be called high-titer samples. Again, 19 of 20 samples that were assayed for spike-specific sIgA and IgG were positive for spike-targeting secretory antibodies. One lacked specific IgA but showed specific secretory antibodies, with another showing the opposite profile. Of these samples positive for spike-specific secretory antibodies, 18 had positive endpoint titers. Meanwhile, among the high-titer spike-specific IgA-containing samples, seven contained high titers of specific secretory antibodies. The levels of IgA and secretory antibodies were positively correlated. Again, 15/20 samples contained spike-directed IgG, and 13 had positive endpoint titers. Only two were high-titer samples. IgA and IgG titers were not correlated, neither were IgG and SC titers. Persistent IgA Response The researchers also observed persistently high spike-targeting IgA titers in 28 paired convalescent samples collected at 4-6 weeks and 4-10 months after infection. The average endpoint titers showed no significant change over this period In half of the samples, the IgA titer was reduced by more than a tenth, of which only two showed over 50% reduction. In 43% it went up by more than a tenth. The longest follow-up was up to 10 months after infection in 14 patients. Here too, the titers were unchanged on the whole, with five donors showing more than 10% drop, eight more than 10% increase, and one with no change. One showed more than a 50% reduction in titer. Neutralizing Activity Neutralizing activity was demonstrated by 75% of samples at the highest concentration, vs. only 13% of controls. The mean percent neutralization values at 50ug/ml were much higher for the convalescent samples relative to the controls. Convalescent samples achieved effective inhibition of 50% of viral particles (50% inhibitory concentration, IC50) in 6/8 samples, but only 1/8 pre-pandemic controls. The mean IC50 among the six convalescent specimens was 33.6ug/mL of total IgA. The neutralizing capacity was correlated significantly with the IgA binding. The two samples that failed to show neutralizing activity also had the lowest IgA endpoint titers. What Are the Implications? The lack of evidence that SARS-CoV-2 is transmitted via human milk has led to recommendations to continue breastfeeding if desired following the delivery of a COIVD-19 positive mother, along with the use of masks, hand and breast hygiene. The current study confirms that breast milk is not just harmless but positively efficacious in providing passive immunity to the infant of a convalescent mother. Not only is the presence of sIgA in milk very common after infection, but is dominant relative to IgG. Moreover, the correlation between anti-spike IgA and secretory antibodies is strong, which shows that the greatest part of breast milk spike-targeting IgA is sIgA, thus effectively protecting the infant. Secretory antibodies are capable of withstanding harsh biological environments such as the gut and the mouth of infants. Extracted milk IgA is also a potential therapeutic avenue for COVID-19, since it will probably survive administration to the airways and will be highly effective at lower doses than those required with the current convalescent plasma or plasma Ig protocols that are administered systemically. While all high-titer IgA-positive samples showed neutralizing activity against the spike, two out of three positive but not high-titer samples failed to do so. These were all from 4-6 week samples, and neutralizing activity may have been detectable as the immune response matured. The durability of the response points towards protection of the infant while on breast milk, and also a potential donor pool to generate extracted milk IgA for therapeutic use. The fact that 8/14 samples at 7-10 months showed a rise rather than a fall in specific IgA titers indicates the possibility of long-lived plasma cells in the GALT and breast tissue. These may be restimulated by other coronaviruses or the same virus on repeated exposure. *Important Notice medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information. To read the original article click here.

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New Biological Antibiotics Can Beat Tuberculosis

AHA Publisher — Mon, 01 Mar 2021 08:00:50 +0000

Brian Blum via Israel21c – Researchers at Tel Aviv University have demonstrated in laboratory mice that monoclonal antibodies can be substituted for antibiotics to hinder the growth of tuberculosis germs. It’s estimated that around a quarter of the world’s population is infected by tuberculosis. In Israel, there are about 200 cases a year. Antibiotics are the usual course of treatment, but antibiotic-resistant strains of tuberculosis are now as high as 40 percent in some countries. Monoclonal antibodies (derived from single cells) have been in the news as one of the most promising “cures” for Covid-19. Antibodies from patients who have recovered from a particular illness can then be injected into a sick person to stimulate the immune system. For the new research, antibodies were isolated from a recovered tuberculosis patient. After the antibodies were introduced to mice infected with tuberculosis, the mice recovered. This marks the first time that researchers have managed to develop a “biological antibiotic” from human antibodies. The study was led by Dr. Natalia Freund and doctoral candidate Avia Watson at Tel Aviv University’s Sackler Medical Faculty, and carried out in collaboration with labs in the United States and China. The results were published in the scientific journal Nature Communications. The use of monoclonal antibodies – the basis behind immunotherapy – has in recent years changed the way physicians treat cancer, autoimmune diseases and viral infections such as Covid-19. “Antibiotics are highly efficacious and cost effective, and therefore for the last years have been our only weapon against bacterial infections,” Freund explains. “Unfortunately, antibiotics become less and less effective, and in the main cases of drug resistance, physicians are empty-handed in finding an appropriate treatment for their patients. Therefore, new ways to kill bacteria are urgently needed.” Freund called the new study “an initial proof-of-concept of employing monoclonal antibodies as an effective therapy in combating bacterial pathogens.” The monoclonal antibodies produced in Freund’s lab work against three different strains of the tuberculous bacteria, and she expects they will be effective against other strains that were not investigated, as well. The antibodies Freund isolated inhibited bacteria growth and reduced bacterial levels by 50% in mice compared with mice that were not treated. “The model that has proven successful in this study will enable us to extend our future work to include other diseases such as pneumonia and staphylococcus infections,” Freund says. To read the original article click here. For more articles from Israel21c click here.

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