Tag Archives: antibodies

New Coronavirus Antibody Test Highly Accurate

Abbott Laboratories’ antibody test for the new coronavirus is highly likely to correctly determine whether people have ever been infected with the fast-spreading virus, the company said, citing a U.S. study.

Researchers at the University of Washington School of Medicine report in the Journal of Clinical Microbiology  that Abbott‘s test had a specificity of 99.9% and a sensitivity of 100%, suggesting very few false positives and no false negatives.

Antibody tests can tell whether a person has ever been infected and are considered crucial in efforts to get Americans back to work safely as the presence of antibodies to the virus indicates possible immunity to future infection.

Abbott’s test was launched last month under the U.S. Food and Drug Administration’s relaxed rules for some coronavirus tests, allowing their distribution before regulatory clearance. It has since received emergency use authorization from the FDA.

Abbott has already shipped more than 10 million antibody tests to hospitals and labs.

Source: bit.ly/2SKTVcQ
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https://www.reuters.com/

Will Llamas Become Coronavirus Killers ?

Antibodies from Winter, a 4-year-old llama with great eyelashes, have neutralized coronavirus and other infections in lab experiments.

Winter is a 4-year-old chocolate-colored llama with spindly legs, ever-so-slightly askew ears and envy-inducing eyelashes. Some scientists hope she might be an important figure in the fight against the novel coronavirus.

She is not a superpowered camelid. Winter was simply the lucky llama chosen by researchers in Belgium, where she lives, to participate in a series of virus studies involving both SARS and MERS. Finding that her antibodies staved off those infections, the scientists posited that those same antibodies could also neutralize the new virus that causes Covid-19. They were right, and published their results in the journal Cell.

Scientists have long turned to llamas for antibody research. In the last decade, for example, scientists have used llamas’ antibodies in H.I.V. and influenza research, finding promising therapies for both viruses.

Humans produce only one kind of antibody, made of two types of protein chains heavy and light — that together form a Y shape. Heavy-chain proteins span the entire Y, while light-chain proteins touch only the Y’s arms. Llamas, on the other hand, produce two types of antibodies. One of those antibodies is similar in size and constitution to human antibodies. But the other is much smaller; it’s only about 25 percent the size of human antibodies. The llama’s antibody still forms a Y, but its arms are much shorter because it doesn’t have any light-chain proteins. This more diminutive antibody can access tinier pockets and crevices on spike proteins — the proteins that allow viruses like the novel coronavirus to break into host cells and infect us — that human antibodies cannot. That can make it more effective in neutralizing virusesLlamas’ antibodies are also easily manipulated, said Dr. Xavier Saelens, a molecular virologist at Ghent University in Belgium and an author of the new study. They can be linked or fused with other antibodies, including human antibodies, and remain stable despite those manipulations.

Source: https://www.cell.com/
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https://www.nytimes.com/

New COVID-19 Vaccine Shows Promise

An experimental COVID-19 vaccine protected monkeys from catching the viral infection, according to an unreviewed report. The new vaccine has now entered clinical trials in China to test the drug in humans.

Although the animal study, posted April 19 to the preprint database bioRxiv, has not been subject to formal review, scientists took to Twitter to share their first impressions.

So, this is the first ‘serious’ preclinical data I have seen for an actual vaccine candidate,” Florian Krammer, a professor in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, tweeted on April 22. Before being tested in healthy humans, vaccines undergo so-called preclinical tests in animals. The experimental vaccine, developed by the Beijing-based company Sinovac Biotech, showed promising results in rhesus macaques before entering human trials, Krammer noted.  “I’m a fan,” he added in another tweet.

Now in clinical trials, various doses of the vaccine will be given to 144 individuals to determine whether it’s safe, meaning it does not cause dangerous side effects, according to ClinicalTrials.gov. The vaccine would then move into efficacy trials with more than 1,000 additional people to determine whether it triggers an adequate immune response, commented Meng Weining, Sinovac’s senior director for overseas regulatory affairs.

The Sinovac vaccine contains an inactivated version of SARS-CoV-2, the virus that causes COVID-19. By introducing an inactive virus into the body, the vaccine should prompt the immune system to build antibodies that target the pathogen without triggering an actual COVID-19 infection. When given to mice, rats and rhesus macaques, the vaccine sparked the production of such antibodies, according to the bioRxiv report. “This is old-fashioned technology,” which would make the product easy to manufacture, Krammer wrote on Twitter. “What I like most is that many vaccine producers, also in lower–middle-income countries, could make such a vaccine,” he added in an interview

Source: http://www.sinovac.com/
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https://www.livescience.com/

Can Plasma From Recovered Covid-19 Patients Cure Infected Others?

US Food and Drug Administration (FDA) officials announced today they have approved plans for nationwide trials of two treatments for Covid-19, the global pandemic disease caused by the new coronavirus—and for their simultaneous use in perhaps hundreds of hospitals.

The therapeutic agents—convalescent plasma and hyperimmune globulin—are both derived from the blood of people who have recovered from the disease, decoctions of the antibodies that the human immune system makes to fight off germs.

 

This is an important area of research—the use of products made from a recovered patient’s blood to potentially treat Covid-19,” said FDA commissioner Stephen Hahn in a release announcing the trials. “The FDA had played a key role in organizing a partnership between industry, academic institutions, and government agencies to facilitate expanded access to convalescent plasma. This is certainly a great example of how we can all come together to take swift action to help the American people during a crisis.”

Physicians are already using a somewhat haphazard collection of antiviral and other drugs for people critically ill with Covid-19, because they don’t have any other options. Nothing—no drug, no vaccine—is approved for use specifically against Covid-19 in the United States, so any new possibility is a hopeful one. Convalescent plasma and hyperimmune globulin join the rarified group of therapeutics that scientists are testing, including a trial of the Ebola drug remdesivir and the much-hyped antimalarial/immune suppressants chloroquine and hydroxychloroquine.

Using blood products from people who’ve already beaten a disease is a century-old approach, predating vaccines and antibiotics. Inspired by its use against polio, two physicians at a Naval hospital in Massachusetts tried it on people who had pneumonia as a result of influenza in 1918, with enough success to warrant more tests. The quality of actual studies of efficacy has varied over the decades, but health care workers used convalescent plasma against SARS, MERS, and Ebola. And a couple of studies—small and preliminary—have shown convalescent plasma having some promise against SARS-CoV-2 as well.

It was all promising enough that the FDA wanted to make sure current patients could have access to the plasma at the same time that researchers were starting a more rigorous investigation. “This seems like ancient history, but maybe it isn’t. There have been niche uses of it for a while,” says Michael Joyner, a physiologist at the Mayo Clinic who in March spearheaded the creation of an ad hoc coalition of researchers interested in pursuing the therapy. Joyner is facilitating the 40-center trial of the new therapies approved today by the FDA, with researchers at Johns Hopkins leading the science. (Joyner himself received gamma globulin, a variant of the treatment, as a preventative against hepatitis B in the 1980s, when he was a medical student.)

At Houston Methodist Hospital, James Musser, the chair of Pathology and Genome Medicine, is a friend of Arturo Casadevall, the Johns Hopkins University immunologist who proposed using convalescent serum early in the pandemic. Musser pushed to get his hospital involved, putting out a call for donors—people who had confirmed positive tests for the virus and had gone at least 14 days without symptoms. His hospital is already doing compassionate-use transfusions. “So far, as of yesterday, we’ve transfused four patients,” Musser said on Thursday. He expected a fifth to receive plasma today. And how’d it work?The truth is, it’s far too early,” Musser says. “We, nationally, need to do controlled trials and understand, first and foremost, is this a safe therapeutic? There’s lots of reasons to think it will be, but you never know.”

Source: https://www.wired.com/

Simple finger-prick tests Coronavirus

Millions of finger-prick coronavirus home-tests could be ready to order on Amazon or pick up in Boots in a matter of days, according to Public Health England (PHE). Sharon Peacock, of PHE‘s National Infection Service, said 3.5million antibody tests the Government has bought will be available in the ‘near future‘.

Asked whether these could be within several days, she told the House of Commons Science and Technology Committeeabsolutely’. However, Professor Peacock did not explain if the test would be free on the NHS or if suspected patients would have to pay. Health chiefs say the tests – which scour a sample of blood for antibodies made by the body to fight the virus – will initially be available for frontline healthcare staff.

The Government’s aim is to get thousands of doctors, nurses and paramedics who have had to self isolate at home as a precaution back to workPHE has not revealed who is manufacturing the tests, which detect if someone has had the infection previously and is now immune.

Personalized cancer vaccines

Therapeutic cancer vaccines were first developed 100 years ago and have remained broadly ineffective to date. Before tangible results can be achieved, two major obstacles must be overcome. Firstly, since tumor mutations are unique to each patient, cancer cell antigens must be targeted extremely precisely, which is very hard to achieve. Secondly, a safe system is needed to deliver the vaccine to the right location and achieve a strong and specific immune response.

Li Tang’s team at EPFL’s School of Engineering in Switzerland is coming up with a solution to the delivery problem. The researchers have used a polymerization technique called polycondensation to develop a prototype vaccine that can travel automatically to the desired location and activate immune cells there. The patented technique has been successfully tested in mice and is the topic of a paper appearing in ACS Central Science. Li Tang has also co-founded a startup called PepGene, with partners that are working on an algorithm for quickly and accurately predicting mutated tumor antigens. Together, the two techniques should result in a new and better cancer vaccine in the next several years.

Helping the body to defend itself

Most vaccines – against measles and tetanus for example – are preventive. Healthy individuals are inoculated with weakened or inactivated parts of a virus, which prompt their immune systems to produce antibodies. This prepares the body to defend itself against future infection.

However, the aim of a therapeutic cancer vaccine is not to prevent the disease, but to help the body defend itself against a disease that is already present. “There are various sorts of immunotherapies other than vaccines, but some patients don’t respond well to them. The vaccine could be combined with those immunotherapies to obtain the best possible immune response,” explains Li Tang. Another advantage is that vaccines should reduce the risk of relapse.

Delivering a cancer vaccine to the immune system involves various stages. First, the patient is inoculated with the vaccine subcutaneously. The vaccine will thus travel to the lymph nodes, where there are lots of immune cells. Once there, the vaccine is expected to penetrate dendritic cells, which act as a kind of alert mechanism. If the vaccine stimulates them correctly, the dendritic cells present specific antigens to cancer-fighting T-cells, a process that activates and trains the T-cells to attack them.

The procedure appears simple, but is extremely hard to put into practice. Because they are very small, the components of a vaccine tend to disperse or be absorbed in the blood stream before reaching the lymph nodes.

To overcome that obstacle, Li Tang has developed a system that chemically binds the vaccine’s parts together to form a larger entity. The new vaccine, named Polycondensate Neoepitope (PNE), consists of neoantigens (mutated antigens specific to the tumor to be attacked) and an adjuvant. When combined within a solvent, the components naturally bind together, forming an entity that is too large to be absorbed by blood vessels and that travels naturally to the lymph nodes.

Source: https://actu.epfl.ch/news/

Nanoparticles Act As Immunotherapy Agents

University of Wisconsin–Madison researchers have developed nanoparticles that, in the lab, can activate immune responses to cancer cells. If they are shown to work as well in the body as they do in the lab, the nanoparticles might provide an effective and more affordable way to fight cancer.

They are cheaper to produce and easier to engineer than the antibodies that underlie current immunotherapies, which as drugs cost tens of thousands of dollars a month.

The nanoparticles were made of sections of the T cell protein PD-1 (in blue) attached to a branched core called a dendrimer (in gray). The branches in the core of the nanoparticle allowed many chunks of the PD-1 protein to bind to the nanoparticle, increasing its effectiveness.

Immunotherapy basically boosts the patient’s own immune system to fight against cancer cells better,” says Seungpyo Hong, a professor in the UW–Madison School of Pharmacy. “The antibodies that are used right now are large, they’re expensive, they’re hard to engineer, and they don’t always show the highest level of efficacy either. So we wanted to explore other ways to activate the immune system.

Hong and postdoctoral associate Woo-jin Jeong led the study, published online Jan. 2 in the Journal of the American Chemical Society, with collaborators at the University of Illinois at Chicago. It’s the first demonstration that nanoparticles can act as immunotherapy agents.

More research is needed to understand their effectiveness in the body, but Hong has applied for a patent on the new nanoparticles and is now testing them in animal models.

In tests against lab-grown strains of cancer, the nanoparticles boosted production of the immune stimulating protein interleukin-2 by T cells, one kind of immune cell in the body, by about 50 percent compared to no treatment. They were just as effective as antibodies. The nanoparticles were also able to improve the effectiveness of the chemotherapy drug doxorubicin in similar tests.

Normally, T cells produce a protein named PD-1 that acts like an off switch for immune responses. This “checkpoint” helps keep T cells from improperly attacking healthy cells.

Source: https://news.wisc.edu/

How To Make Cells Immune To HIV

Some viruses, no matter how hard we try, remain resistant to vaccines. Now, researchers are using a different method, gene editing, as a way to make cells immune to mankind’s most difficult viruses. Led by Dr. Justin Taylor, a team at the Fred Hutchinson Cancer Research Center has targeted four infections for which there’s no protective vaccine: HIV, influenza, the Epstein-Barr virus (EBV) and respiratory syncytial virus (RSV).

The researchers used CRISPR/Cas9 technology to modify B cells, a class of white blood cells that produce antibodies to protect us from diseases. By coding the cells with genes that create specific antibodies, the team was able to make them immune without the use of a vaccine.

The researchers tested the method in both human cells in a test tube and in living mice. On average, about 30 percent of the cells produced the desired antibody. Taylor said that the mice remained protected for 83 days following the procedure, an important benchmark given that patients who receive stem cell transplants can have weakened immune systems for three to six months. To be clear, Taylor doesn’t have anything against traditional vaccination. “Vaccines are great,” he said. “I wish we had more of them.”

Instead, Taylor thinks the gene editing method could work one day for diseases where we don’t have a vaccine. It may help patients who are immuno-compromised, meaning their bodies can no longer fight infections, as well as older patients whose bodies aren’t as receptive to vaccines. Gene-edited immunity might also be used to protect people faster than can be done with traditional vaccines, which could be useful during unexpected outbreaks.

Taylor’s team included Fred Hutch researchers and co-authors Howell Moffett, Carson Harms, Kristin Fitzpatrick, Marti Tooley and Jim Boonyaratanakornkit. The results will be published in the journal Science Immunology.

Source: https://www.fredhutch.org/
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https://www.geekwire.com/

Early-Stage Detection Of Alzheimer’s In The Blood

Two major studies with promising antibodies have recently failed – possibly because they have been administered too late. A new very early-detection test gives rise to hope. Using current techniques, Alzheimer’s disease, the most frequent cause of dementia, can only be detected once the typical plaques have formed in the brain. At this point, therapy seems no longer possible. However, the first changes caused by Alzheimer’s take place on the protein level up to 20 years sooner. A two-tier method developed at Ruhr-Universität Bochum (RUB) can help detect the disease at a much earlier stage. The researchers from Bochum published their report in the March 2019 edition of the journal “Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring”.

This has paved the way for early-stage therapy approaches, where the as yet inefficient drugs on which we had pinned our hopes may prove effective,” says Professor Klaus Gerwert from the Department of Biophysics at RUB.

In Alzheimer’s patients, the amyloid beta protein folds incorrectly due to pathological changes long before the first symptoms occur. A team of researchers headed by Klaus Gerwert successfully diagnosed this misfolding using a simple blood test; as a result, the disease can be detected approximately eight years before the first clinical symptoms occur. The test wasn’t suitable for clinical applications however: it did detect 71 per cent of Alzheimer’s cases in symptomless stages, but at the same time provided false positive diagnoses for nine per cent of the study participants. In order to increase the number of correctly identified Alzheimer’s cases and to reduce the number of false positive diagnoses, the researchers poured a lot of time and effort into optimising the test.

As a result, they have now introduced the two-tier diagnostic method. To this end, they use the original blood test to identify high-risk individuals. Subsequently, they add a dementia-specific biomarker, namely tau protein, to run further tests with those test participants whose Alzheimer’s diagnosis was positive in the first step. If both biomarkers show a positive result, there is a high likelihood of Alzheimer’s disease. “Through the combination of both analyses, 87 of 100 Alzheimer’s patients were correctly identified in our study,” summarises Klaus Gerwert. “And we reduced the number of false positive diagnoses in healthy subjects to 3 of 100. The second analysis is carried out in cerebrospinal fluid that is extracted from the spinal cord.

Now, new clinical studies with test participants in very early stages of the disease can be launched,” points out Gerwert. He is hoping that the existing therapeutic antibodies will still have an effect. “Recently, two major promising studies have failed, especially Crenezumab and Aducanumab – not least because it had probably already been too late by the time therapy was taken up. The new test opens up a new therapy window.”

Source: https://news.rub.de/