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By engineering a short chunk of protein, or peptide, that can prevent the attachment of human parainfluenza viruses to cells, researchers have improved a method in rodent models intended to help keep children healthy.
Human parainfluenza viruses, or HPIVs, are the leading cause of childhood respiratory infections, responsible for 30% to 40% of illnesses like croup and pneumonia. The viruses also affect the elderly and people with compromised immune systems.
To sicken people, HPIVs must latch onto cells and inject their genetic material to start making new viruses. HPIV3 is the most prevalent among these viruses. There are currently no approved vaccines or antivirals for HPIV3 infection in people.
In a study led by the Sam Gellman lab in the chemistry department at the University of Wisconsin-Madison, and the lab of Anne Moscona and Matteo Porotto at Columbia University, researchers built upon years of work on peptide treatments to generate one capable of blocking the HPIV3 attachment process.
The researchers published their findings April 7 in the Journal of the American Chemical Society.
To enter host cells, HPIVs use specialized fusion proteins that resemble three corkscrews laid side-by-side. Earlier work by the Moscona-Porotto lab showed that scientists could a partial chunk of this corkscrew protein from HPIV3, introduce this peptide to the virus, and prevent the corkscrew from driving the infection process. The peptide, itself a corkscrew, essentially zippers up with the virus’s corkscrews, creating a tight bundle of six corkscrew shapes.

It is well known that each person’s gut bacteria is vital for digestion and overall health, but when does that gut microbiome start?
New research led by scientists from McMaster University and Charité — Universitätsmedizin Berlin in Germany has found it happens during and after birth, and not before.
McMaster researchers Deborah Sloboda and Katherine Kennedy examined prenatal stool (meconium) samples collected from 20 babies during breech Cesarean delivery.
“The key takeaway from our study is we are not colonized before birth. Rather, our relationship with our gut bacteria emerges after birth and during infancy,” said Kennedy, first author of the study and a PhD student, whose findings are published in Nature Microbiology.
Recent studies have sparked controversy by claiming that we are colonized by gut bacteria before birth. But, Kennedy said, studies such as these have been criticized for the ways they control for contamination.
“By including only breech caesarean deliveries in healthy pregnant women we were able to avoid the transmission of bacteria that occurs naturally during a vaginal birth,” said Thorsten Braun, co-senior author and lead obstetric consultant and deputy director of the Department of ‘Experimental Obstetrics’ at Charité — Universitätsmedizin Berlin.
Kennedy said recent data suggest that a person’s relationship with their own gut bacteria is most important in early life, during critical stages of immunological and physiological development.
Sloboda, co-senior author, agrees.
“The fact that colonization of infants’ guts occurs during and after their births, means that not only is it vulnerable to early environmental influences, but could also offers a window of potential intervention,” said Sloboda, professor of biochemistry and biomedical sciences at McMaster and the Canada Research Chair in perinatal programming.
“While many of the exact mechanisms surrounding gut bacteria and their role in our early development is unclear, discovering when and how we are colonized is a key first step.”
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New variants of the SARS-CoV-2 virus most likely will necessitate the development of more vaccine options in the years ahead, and a biomedical scientist at Iowa State University believes the “key” to that development lies in the way the virus binds to human cells.
Michael Cho, a professor of biomedical sciences at Iowa State, is studying how to develop COVID-19 vaccines that target SARS-CoV-2’s receptor-binding domain, or the part of the virus that docks with the host cellular receptor, angiotensin converting enzyme 2 (ACE2). This docking process allows the virus access to the host’s cells, which leads to infection.
Cho was the lead author of a study recently published in the peer-reviewed scientific journal Frontiers in Immunology detailing the ability of a vaccine to induce antibodies in mice that target the virus’s receptor binding domain. The patent-pending vaccine approach is available for licensing from the Iowa State University Research Foundation. Cho will deliver a virtual presentation on the potential of the approach to BioConnect Iowa’s vaccine and immunotherapeutics meeting on Wednesday.
The antibodies produced by the experimental vaccine attack the receptor binding domain, or RBD, of the virus. The RBD is the portion of the viral spike protein that binds to host cells to initiate infection. Cho likens the spike protein to a key, and the RBD is the part of the key that actually enters the lock.
“The spike glycoprotein is the key that opens the lock, and the region of the key with all the peaks and valleys and grooves is the RBD,” Cho said. “If antibodies attack the RBD, then the key won’t work and the door will stay locked, preventing infection. We don’t really need to make antibodies against the entire spike protein, which is more difficult to make. We can just focus on the RBD portion.”
This approach differs from the three vaccines currently available in the United States to ward off COVID-19. The mRNA vaccines produced by Pfizer and Moderna work by delivering a set of instructions that teach the immune system how to make the entire spike protein that triggers an immune response. The Johnson & Johnson vaccine is known as a viral vector vaccine that uses a modified version of a different virus.
Cho and his colleagues conducted trials of the RBD subunit protein vaccine on mice and were able to induce a potent antibody response in the rodents over the course of three injections. The study showed that one or two injections are sufficient, depending on the adjuvant used. Cho said he would like to test the approach in human trials.
Easy to produce, scale up
The RBD-targeting vaccine has some advantages over the vaccines currently licensed for use in the United States. Cho said the experimental vaccine is relatively easy to produce and scale up because it requires only a small portion of the virus’s spike protein to manufacture. The RBD vaccine also can be delivered multiple times, which could be necessary to develop immunity against multiple virus variants that will inevitably emerge.
Cho said the process of reaching herd immunity to COVID-19 through vaccines will take time, allowing for new variants of the virus to spread. This is particularly true for populations in developing countries that have had only limited access to the currently available vaccines so far. And as more variants emerge, the likelihood grows that additional vaccines will become necessary, he said.
“Just because we have vaccines now, that doesn’t mean we won’t need more in three or five years, maybe even longer,” he said. “I don’t think our vaccine is too late to play a role.”
The 2021 Immunotherapeutics Virtual Conference is presented by Iowa State, the University of Iowa and BioConnect Iowa. The conference aims to connect cutting-edge university research with industry leaders. Cho will address the virtual conference Wednesday morning.
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Scientists have discovered that many esophageal cancers turn on ancient viral DNA that was embedded in our genome hundreds of millions of years ago.
“It was surprising,” says Adam Bass, MD, the Herbert and Florence Irving Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, who led the study published May 10 in Nature Genetics.
“We weren’t specifically searching for the viral elements, but the finding opens up a huge new array of potential cancer targets that I think will be extremely exciting as ways to enhance immunotherapy.”
Fossil Viruses and Cancer
The idea that bits of ancient retroviruses within the human genome — known as endogenous retroviral elements, or ERVs — play a role in cancer is not new. Though ERV sequences have degraded over time and cannot produce viral particles, the viral fossils are sometimes inserted into other genes, which disrupts their normal activities, or act as switches that turn on cancer-causing genes.
More recently, however, research suggests ERVs may also fight cancer if they are transcribed into strands of RNA.

Severe cases of COVID-19 can now be detected at an early stage. Researchers at the University of Zurich have identified the first biomarker that can reliably predict which patients will develop severe symptoms. This can help to improve the treatment of severe cases of COVID-19.
Most people who are infected with SARS-CoV-2 develop no or only mild symptoms. However, some patients suffer severe life-threatening cases of COVID-19 and require intensive medical care and a ventilator to help them breathe. Many of these patients eventually succumb to the disease or suffer significant long-term health consequences. To identify and treat these patients at an early stage, a kind of “measuring stick” is needed — predictive biomarkers that can recognize those who are at risk of developing severe COVID-19.
First biomarker to predict severity of disease
A team led by Professor Burkhard Becher at the Institute of Experimental Immunology at the University of Zurich, working with researchers from Tübingen, Toulouse and Nantes, has now discovered such a biomarker — the number of natural killer T cells in the blood. These cells are a type of white blood cell and part of the early immune response. “The number of natural killer T cells in the blood can be used to predict severe cases of COVID-19 with a high degree of certainty — even on a patient’s first day in hospital,” says Burkhard Becher.
Targeted therapy thanks to precise immunopathogenesis
The new biomarker test helps clinicians decide which organizational and treatment measures need to be taken for patients with COVID-19, such as transfer to the ICU, frequency of oxygen measurements, type of therapy and treatment start. “Predictive biomarkers are very useful for making these decisions. They help clinicians provide patients suffering severe symptoms with the best care possible,” says Stefanie Kreutmair, first author of the study. “Our findings also make it possible to investigate new therapies against COVID-19.”
With the help of high-tech
The rapid deterioration in the health of COVID-19 patients is caused by an overreaction of the body’s immune system. “The body produces small proteins called cytokines at a much higher rate, which leads to a ‘cytokine storm’ and triggers massive inflammation. Immune cells invade the lungs, where they disrupt gas exchange,” explains Becher. To detect the immune cells and cytokines in patient samples, the UZH researchers used high-dimensional cytometry. This technology enables researchers to characterize many surface and intracellular proteins in millions of individual cells and process them using computer algorithms.
SARS-CoV-2-specific immune signature deciphered
Many other pathogens besides SARS-CoV-2 can cause pneumonia — and thus spark an immune response. The immune response triggered by COVID-19 has been studied extensively, but the exact nature of the immune response to SARS-CoV-2 has, to date, been unclear. To characterize this response, the researchers also analyzed blood samples of patients with severe pneumonia driven by a pathogen other than the novel coronavirus. By comparing the immune responses in COVID-19 patients with those of the control group, the researchers were able to determine the unique characteristics of the SARS-CoV-2 immune response.
“The immune responses to the various pneumonias are very similar and part of the body’s general inflammatory response, as often observed in patients in intensive care. When it comes to COVID-19, however, T cells and natural killer cells display a unique behavior and describe a kind of pattern in the immune system — the immune signature specific to COVID-19,” explains Becher.
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Researchers at KU Leuven (Belgium) have developed a 3D printing technique that extends the possibilities of lateral flow testing. These tests are widespread in the form of the classic pregnancy test and the COVID-19 self-tests. With the new printing technique, advanced diagnostic tests can be produced that are quick, cheap, and easy to use.
The COVID-19 pandemic has made everyone aware of the importance of rapid diagnosis. The sale of self-tests in pharmacies has been permitted in Belgium since the end of March. This self-test is a so-called lateral flow test. Using a wiper, a sample is taken through the nose. Next, it is dissolved in a solvent, and applied to the test kit. Absorbent material in the kit moves the sample downstream and brings it in contact with an antibody. If virus is present, a coloured line appears. The advantage of these tests is that they are cheap and do not require any specialised appliances.
Lateral flow tests are useful for simple tests that result in a yes-no answer, but not for tests that require a multi-step protocol. That is why bioengineers at KU Leuven set out to develop a new type of lateral flow test with more capabilities.
Precise prints
Using a 3D printer, the researchers fabricated a 3D version of a lateral flow test. The basis is a small block of porous polymer, in which ‘inks’ with specific properties are printed at precise locations. In this way, a network of channels and small ‘locks’ is printed that let the flow through or block it where and when necessary, without the need for moving parts. During the test, the sample is automatically guided through the different test steps. That way, even complex protocols can be followed.
The researchers evaluated their technique reproducing an ELISA test (Enzyme-Linked Immunosorbent Assay), which is used to detect immunoglobulin E (IgE). Ig E is measured to diagnose allergies. In the lab, this test requires several steps, with different rinses and a change in acidity. The research team was able to run this entire protocol using a printed test kit the size of a thick credit card.
Complexity is not a cost
“The great thing about 3D printing is that you can quickly adapt a test’s design to accommodate another protocol, for example, to detect a cancer biomarker. For the 3D printer it does not matter how complex the network of channels is,” says Dr. Cesar Parra. The 3D printing technique is also affordable and scalable. “In our lab, producing the Ig E prototype test costs about $ 1.50, but if we can scale it up, it would be less than $ 1,” says Dr. Parra. The technique not only offers opportunities for cheaper and faster diagnosis in developed countries, but also in countries where the medical infrastructure is less accessible and where there is a strong need for affordable diagnostic tests.
The research group is currently designing its own 3D printer, which will be more flexible than the commercial model used in the current study. “An optimised printer is kind of like a mobile mini factory which can quickly produce diagnostics. You could then create different types of tests by simply loading a different design file and ink. We want to continue our research on diagnostic challenges and applications with the help of partners,” concludes innovation manager Bart van Duffel.
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A potential new vaccine developed by members of the Duke Human Vaccine Institute has proven effective in protecting monkeys and mice from a variety of coronavirus infections — including SARS-CoV-2 as well as the original SARS-CoV-1 and related bat coronaviruses that could potentially cause the next pandemic.
The new vaccine, called a pan-coronavirus vaccine, triggers neutralizing antibodies via a nanoparticle. The nanoparticle is composed of the coronavirus part that allows it to bind to the body’s cell receptors and is formulated with a chemical booster called an adjuvant. Success in primates is highly relevant to humans.
The findings appear Monday, May 10, in the journal Nature.
“We began this work last spring with the understanding that, like all viruses, mutations would occur in the SARS-CoV-2 virus, which causes COVID-19,” said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI). “The mRNA vaccines were already under development, so we were looking for ways to sustain their efficacy once those variants appeared.
“This approach not only provided protection against SARS-CoV-2, but the antibodies induced by the vaccine also neutralized variants of concern that originated in the United Kingdom, South Africa and Brazil,” Haynes said. “And the induced antibodies reacted with quite a large panel of coronaviruses.”
Haynes and colleagues, including lead author Kevin Saunders, Ph.D., director of research at DHVI, built on earlier studies involving SARS, the respiratory illness caused by a coronavirus called SARS-CoV-1. They found a person who had been infected with SARS developed antibodies capable of neutralizing multiple coronaviruses, suggesting that a pan-coronavirus might be possible.

When a cell is infected, SARS-CoV-2 not only causes the host cell to produce new virus particles. The virus also suppresses host cell defence mechanisms. The virus protein nsP3 plays a central role in this. Using structural analyses, researchers at Goethe University in cooperation with the Swiss Paul Scherrer Institute have now discovered that a decomposition product of the virostatic agent remdesivir binds to nsP3. This points to a further, previously unknown effective mechanism of remdesivir which may be important for the development of new drugs to combat SARS-CoV-2 and other RNA viruses.
The virostatic agent remdesivir was developed to disrupt an important step in the propagation of RNA viruses, to which SARS-CoV-2 also belongs: the reproduction of the virus’s own genetic material. This is present as RNA matrices with which the host cell directly produces virus proteins. To accelerate the production of its own proteins, however, RNA viruses cause the RNA matrices to be copied. To do so, they use a specific protein of their own (an RNA polymerase), which is blocked by remdesivir. Strictly speaking, remdesivir does not do this itself, but rather a substance that is synthesized from remdesivir in five steps when remdesivir penetrates a cell.
In the second of these five steps, an intermediate is formed from remdesivir, a substance with the somewhat unwieldy name GS-441524 (in scientific terms: a remdesivir metabolite). GS-441524 is a virostatic agent as well. As the scientists in the group headed by Professor Stefan Knapp from the Institute for Pharmaceutical Chemistry at Goethe University Frankfurt have discovered, GS-441524 targets a SARS-CoV-2 protein called nsP3. nsP3 is a multifunctional protein, whose tasks include suppressing the host cell’s defence response. The host cell is not helpless in the face of a virus attack, but activates inflammatory mechanisms, among other things, to summon the aid of the cell’s endogenous immune system. nsP3 helps the viruses suppress the cell’s calls for help.
Professor Stefan Knapp explains: “GS-441525 inhibits the activities of an nsP3 domain which is important for the reproduction of viruses, and which communicates with human cellular defence systems. Our structural analysis shows how this inhibition functions, allowing us to lay an important foundation for the development of new and more potent antiviral drugs — effective not only against SARS-CoV-2. The target structure of GS-441524 is very similar in other coronaviruses, for example SARS-CoV and MERS-CoV, as well in a series of alphaviruses, such as the chikungunya virus. For this reason, the development of such medicines could also help prepare for future virus pandemics.”
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MRSA skin infections are often treated with intravenous injection of antibiotics, which can cause significant side effects and promote the development of resistant bacterial strains. To solve these problems, researchers at Karolinska Institutet in Sweden are developing a microneedle patch that delivers antibiotics directly into the affected skin area. New results published in Advanced Materials Technologies show that the microneedle patch effectively reduces MRSA bacteria in the skin.
MRSA (methicillin resistant Staphylococcus aureus) skin infections are potentially lethal, especially in patients with compromised immune systems. Vancomycin is one of the main treatments and is given as an intravenous injection. The reason the antibiotic is not given locally is because of its low ability to penetrate the skin. It is not given orally either because of poor absorption through the gut. The problem with systemic administration is that it often results in significant side effects. Moreover, even when relatively high doses are administered, the local concentration of vancomycin in the skin remains low, which may promote the development of antibiotic resistant strains. Thus, there is a clinical need for local delivery of vancomycin to the skin.
“We have addressed this by using microneedle patches that consist of miniaturised needles made from a polymer that is loaded with the drug,” says Jill Ziesmer, PhD student at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet and first author of the study. “Through an innovative microneedle design we could efficiently control the drug amounts delivered into the skin.”
The patch is placed on the skin at the site of infection. The barely visible microneedles are so small that they do not reach the pain receptors, which makes the treatment relatively painless. The microneedles’ ability to penetrate the skin was studied in skin tissue from piglets and excised human skin. The results show that the drug was effectively delivered into the skin, and most importantly, significantly reduced the MRSA bacterial population.
“If this drug delivery device reaches the clinics, it has the capacity to transform the way skin infections from potentially lethal bacteria are treated with drastic improvements in the quality of life of patients,” says Georgios Sotiriou, principal researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet and last author of the study.
The researchers will now evaluate the performance of microneedles in animal models of MRSA skin infection. The next step is to further develop the product so that it exerts antimicrobial activity through multiple modes of action in order to improve efficacy.
Microneedles were voted one of the top 10 emerging technologies by World Economic Forum in 2020. They are already in clinical use for administering vaccines and there are many ongoing clinical trials for other uses such as treating diabetes, cancer and neuropathic pain.
“Microneedles for delivery of antibiotics have only been studied recently, however, the successful application of microneedles in other areas gives hope that antibiotic microneedles might open new frontiers in skin infection management,” says Georgios Sotiriou.
The research has received funding from the European Research Council (ERC), NordForsk, the Faculty Board at Karolinska Institutet, the Swedish Research Council, the Torsten Söderberg Foundation and the Swedish Foundation for Strategic Research.
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