Inhalable ‘SHIELD’ Protects Lungs Against COVID-19, Flu Viruses

Photo Credit: Robina Weermeijer

Researchers have developed an inhalable powder that could protect lungs and airways from viral invasion by reinforcing the body’s own mucosal layer. The powder, called Spherical Hydrogel Inhalation for Enhanced Lung Defense, or SHIELD, reduced infection in both mouse and non-human primate models over a 24-hour period, and can be taken repeatedly without affecting normal lung function.

“The idea behind this work is simple – viruses have to penetrate the mucus in order to reach and infect the cells, so we’ve created an inhalable bioadhesive that combines with your own mucus to prevent viruses from getting to your lung cells,” says Ke Cheng, corresponding author of the paper describing the work. “Mucus is the body’s natural hydrogel barrier; we are just enhancing that barrier.”

Cheng is the Randall B. Terry, Jr. Distinguished Professor in Regenerative Medicine at North Carolina State University’s College of Veterinary Medicine and a professor in the NC State/UNC-Chapel Hill Joint Department of Biomedical Engineering.

The inhalable powder microparticles are composed of gelatin and poly(acrylic acid) grafted with a non-toxic ester. When introduced to a moist environment – such as the respiratory tract and lungs – the microparticles swell and adhere to the mucosal layer, increasing the “stickiness” of the mucus.

How hepatitis E viruses penetrate cells

It was only around three years ago that a cell culture model was developed that can be used to examine hepatitis E exactly in the laboratory.
Photo Credit: RUB, Marquar

A certain surface protein is important for the cell entry of the hepatitis E virus. Medicines can suppress it.

Although hepatitis E is a common disease, little is known about the life cycle of the virus. A team from Molecular and Medical Virology at the Ruhr University Bochum and Carl von Ossietzky University Oldenburg reports on initial findings on how he manages to infect cells in the journal Hepatology from 7. February 2023. A protein called EGFR, short for Epidermal Growth Factor Receptor, plays a decisive role in the penetration of virus particles into cells. This finding could open up new treatment routes for hepatitis E. Because there are already approved drugs against EGFR that inhibit the activity of this receptor.

Cell culture model makes investigations possible

One of the reasons why hepatitis E has been researched comparatively little is that it was only around three years ago in Bochum and Hanover a robust cell culture model has been developed for its investigation is. Using this model, the researchers were now able to investigate how the virus manages to infect cells.

"With medication, we suppressed the activity of the EGFR protein at the time the virus entered some cell lines," explains first author Jil Alexandra Schrader. “With these cultures, we could see that there were significantly fewer infected cells." The researchers used cell cultures as a cross-check, in which the co-receptor was produced in excess. In this case, there were more infections than untreated cells.

Deer carry SARS-CoV-2 variants that are extinct in humans

White-tailed deer
Photo Credit: Heidi-Ann Fourkiller | SFLORG

White-tailed deer ­– the most abundant large mammal in North America – are harboring SARS-CoV-2 variants that once widely circulated but are no longer found in humans.

Whether or not deer could act as long-term reservoirs for these variants that have become obsolete in people is unknown, as scientists need more time and study to verify if it’s true.

The study, “White-tailed Deer (Odocoileus virginianus) May Serve as a Wildlife Reservoir for Nearly Extinct SARS-CoV-2 Variants of Concern,” which published Jan. 31 in the journal Proceedings of the National Academy of Sciences, represents one of the most comprehensive studies to date to assess the prevalence, genetic diversity and evolution of SARS-CoV-2 in white-tailed deer. The study focused on the white-tailed deer population in New York.

“One of the most striking findings of this study was the detection of co-circulation of three variants of concern – alpha, gamma and delta – in this wild animal population,” said Dr. Diego Diel, associate professor in the Department of Population Medicine and Diagnostic Sciences and director of the Virology Laboratory at the College of Veterinary Medicine’s (CVM) Animal Health Diagnostic Center. 

Over the course of the pandemic, deer have become infected with SARS-CoV-2 through ongoing contact with humans, possibly from hunting, wildlife rehabilitations, feeding of wild animals or through wastewater or water sources, though no one knows for sure.

Scientists Document Two Separate Reservoirs of Latent HIV in Patients

Rebound DNA sequences from the blood (red) and the CSF (blue)
Illustration Credit: Ron Swanstrom | UNC Center for AIDS Research | Swanstrom lab

This research, led by UNC School of Medicine scientists Laura Kincer, Sarah Joseph, PhD, and Ron Swanstrom, PhD, with international collaborators, shows that in addition to HIV’s ability to lay dormant in the blood/lymphoid system, the virus may also lay dormant in the central nervous system, delineating another challenge in creating a cure.

When people living with HIV take antiviral therapy (ART), their viral loads are driven so low that a standard blood test cannot detect the virus. However, once ART is stopped, detectable HIV re-emerges with new cells getting infected. This is called “rebound” virus, and the cells that release the virus to re-ignite the infection come from a small population of HIV-infected CD4+ T cells that had remained dormant in blood and lymph tissue while individuals were on ART.

It’s a problem called latency, and overcoming it remains a major goal for researchers trying to create curative therapies for HIV—the special focus of the UNC HIV Cure Center.

Marburg vaccine shows promising results in first-in-human study

Colorized scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (orange).
Image Credit: National Institute of Allergy and Infectious Diseases

A newly published paper in The Lancet shows that an experimental vaccine against Marburg virus (MARV) was safe and induced an immune response in a small, first-in-human clinical trial. The vaccine, developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, could someday be an important tool to respond to Marburg virus outbreaks.

This first-in-human, Phase 1 study tested an experimental MARV vaccine candidate, known as cAd3-Marburg, which was developed at NIAID’s Vaccine Research Center (VRC). This vaccine uses a modified chimpanzee adenovirus called cAd3, which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MARV to induce immune responses against the virus. The cAd3 vaccine platform demonstrated a good safety profile in prior clinical trials when used in investigational Ebola virus and Sudan virus vaccines developed by the VRC.

New virus discovered in whales, dolphins across the Pacific

Photo Credit: Richard Sagredo

A novel virus, potentially fatal to whales and dolphins, has been discovered by researchers at the University of Hawaiʻi Health and Stranding Lab. Prior to its discovery in 10 whale and dolphin host species across the Pacific, the virus was found in only a single marine mammal worldwide, a Longman’s beaked whale stranded on Maui in 2010. The findings were published in Frontiers in Marine Science.

The discovery of beaked whale circovirus (BWCV) in whales and dolphins expands the knowledge of marine mammal species that can become infected with the disease. Circoviruses are DNA viruses that cause disease in birds, pigs and dogs, and in severe cases can become fatal.

“Our study found Cuvier’s beaked whales tested positive for BWCV in Saipan and American Samoa, nearly 4,000 miles away from the first discovered case,” said Kristi West, director of the UH Health and Stranding Lab. “The positive cases found outside of Hawaiʻi were surprising, and indicates that this virus is spread across the Central and Western Pacific and may have a global presence in marine mammals.”

Highly accurate test for common respiratory viruses uses DNA as ‘bait’

Doctor examining a patient
Photo Credit: Thirdman

The test uses DNA ‘nanobait’ to detect the most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. The results are reported in the journal Nature Nanotechnology.

The winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

Mucosal antibodies in the airways provide durable protection against SARS-CoV-2

Charlotte Thålin, M.D. and associate professor at the Department of Clinical Sciences, Danderyd Hospital
Photo Credit: Ludvig Kostyal

Researchers hope that a nasal vaccine may generate mucosal immune responses that protect against SARS-CoV-2 infection.

High levels of mucosal IgA antibodies in the airways protect against SARS-CoV-2 infection for at least eight months. Omicron infection generates durable mucosal antibodies, reducing the risk of re-infection. These are the findings of a study published in The Lancet Infectious Diseases by researchers at Karolinska Institutet and Danderyd Hospital in Sweden. The results raise further hope for the feasibility of future nasal vaccine platforms to protect against infection.

“Antibodies in the blood protect from severe disease, but if we aim to limit infection, viral transmission and the emergence of new SARS-CoV-2 variants, we need to reinforce our immunity at the mucosal surface, which is the viral point of entry”, says Charlotte Thålin, M.D. and associate professor at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet who led the study. “This is not achieved by currently employed intramuscularly-delivered vaccines. But the hope is that a nasal vaccine may generate mucosal immune responses similar to those seen after infection, and thereby block the transmission chain”.

Monkeypox viruses remain sensitive to the available drugs

Monkeypox Virus
Illustration Credit: Samuel F. Johanns

The three antiviral drugs commonly used to treat mpox viruses (monkeypox viruses) are also effective against the viruses from the current outbreak. This has been shown in cell culture experiments by scientists at Goethe University Frankfurt/University Hospital Frankfurt and the University of Kent in Canterbury, Great Britain.

The mpox virus is closely related to the smallpox virus (variola virus), which caused large, deadly outbreaks before it was eradicated by vaccination at the end of the 1970s. While the smallpox virus led to very severe disease progression with a death rate of about 30 percent, mpox is milder. Nevertheless, the mortality rate is still about three percent. Particularly at risk of a severe course of the disease are people with a weakened immune system, elderly persons, pregnant women, newborn babies and young children. Until recently, mpox outbreaks only occurred in certain parts of Africa when humans became infected through contact with wild animals, typically rodents such as the Gambian pouched rat and the rope squirrel.

However, in May 2022 a first large mpox outbreak outside Africa was detected; the virus spread solely through human-to-human transmission. This ongoing outbreak has so far reached more than 100 countries and been classified by the World Health Organization (WHO) as a "Public Health Emergency of International Concern".

Effects of highly pathogenic avian influenza on canids investigated

When the H5N1 HPAI virus (orange) affected a flock of crows in a public garden, it caused a mass die-off of crows. An Ezo red fox and a Japanese raccoon dog were also infected by the H5N1 HPAI virus, the former likely by consuming corpses of the crows, and the latter due to close contact with crow corpses
Illustration Credit: Takahiro Hiono

Researchers at Hokkaido University have revealed the effects of high pathogenicity avian influenza virus infection on an Ezo red fox and a Japanese raccoon dog, linking their infection to a recorded die-off of crows.

High Pathogenicity Avian Influenza (HPAI), commonly known as a type of bird flu, is caused by a group of influenza viruses that affect birds. Humans are very rarely infected by this virus. The most well-known HPAI viral subtype is H5N1, first reported in 1996 for its infection in geese, and then found in humans since 1997. A great amount of time and resources are devoted to monitoring and tracking the spread of HPAI across the globe, due to its disruptive potential on poultry farming—outbreaks are contained by culling exposed and infected flocks.

Quenchbody Immunosensors Pave the Way to Quick and Sensitive COVID-19 Diagnostics

A new immunosensor based on Quenchbody technology shows great potential as a fast, inexpensive, and convenient tool to detect SARS-CoV-2. Developed by scientists at Tokyo Institute of Technology (Tokyo Tech) and Tokyo Medical and Dental University (TMDU), this highly efficient diagnostic approach will be useful not only for point-of-care testing, but also for high-throughput epidemiological studies of COVID-19 and other emerging infectious diseases.

The double-tagged Quenchbody immunosensor becomes fluorescent when its target antigen—the nucleocapsid protein from SARS-CoV-2—binds at the antigen-binding region of the antibody fragments. This approach is fast, cost-effective, and convenient to use in practice, making it ideal for point-of-care testing as well as batch processing of patient samples. 

The incredibly fast spread of COVID-19 throughout the world brought to light a very important fact: we need better methods to diagnose infectious diseases quickly and efficiently. During the early months of the pandemic, polymerase chain reaction (PCR) tests were one of the most widely used techniques to detect COVID-19. However, these viral RNA-based techniques require expensive equipment and reaction times longer than an hour, which renders them less than ideal for point-of-care testing.

Studies find Omicron related hospitalizations lower in severity than Delta and Pfizer-BioNTech COVID vaccine remains effective in preventing hospitalizations

Photo Credit: Fernando Zhiminaicela

Adult hospitalizations from Omicron-related SARS-CoV-2 (COVID-19) were less severe than Delta and the Pfizer-BioNTech vaccine (also known as Comirnaty and BNT162b2*) remains effective in preventing not only hospitalization, but severe patient outcomes associated with COVID-19, two new research studies have found.

The University of Bristol-led research, funded and conducted in collaboration with Pfizer Inc., as part of AvonCAP, is published in The Lancet Regional Health – Europe.

AvonCAP records adults who are admitted to Bristol’s two hospital Trusts – North Bristol NHS Trust (NBT) and University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) with possible respiratory infection.

In the first paper ‘Severity of Omicron (B.1.1.529) and Delta (B.1.617.2) SARS-CoV-2 infection among hospitalized adults: a prospective cohort study in Bristol, United Kingdom’ researchers assessed whether Delta SARS-CoV-2 infection resulted in worse patient outcomes than Omicron SARS-CoV-2 infection, in hospitalized patients

The study aimed to provide more detailed data on patient outcomes, such as the need for respiratory support.

How a viral toxin may exacerbate severe COVID-19

In a new study, University of California, Berkeley, researchers find that portions of the SARS-CoV-2 “spike” protein, shown in the foreground, can damage the cell barriers that line the inside of blood vessels, contributing to some of COVID-19’s most dangerous symptoms, including acute respiratory distress syndrome (ARDS).
Image Credit: National Institutes of Health

In a new study, University of California, Berkeley, researchers find that portions of the SARS-CoV-2 “spike” protein, shown in the foreground, can damage the cell barriers that line the inside of blood vessels, contributing to some of COVID-19’s most dangerous symptoms, including acute respiratory distress syndrome (ARDS). (National Institutes of Health photo via Flickr)

A study published today in the journal Nature Communications reveals how a viral toxin produced by the SARS-CoV-2 virus may contribute to severe COVID-19 infections.

The study shows how a portion of the SARS-CoV-2 “spike” protein can damage cell barriers that line the inside of blood vessels within organs of the body, such as the lungs, contributing to what is known as vascular leak. Blocking the activity of this protein may help prevent some of COVID-19’s deadliest symptoms, including pulmonary edema, which contributes to acute respiratory distress syndrome (ARDS).

“In theory, by specifically targeting this pathway, we could block pathogenesis that leads to vascular disorder and acute respiratory distress syndrome without needing to target the virus itself,” said study lead author Scott Biering, a postdoctoral scholar at the University of California, Berkeley. “In light of all the different variants that are emerging and the difficulty in preventing infection from each one individually, it might be beneficial to focus on these triggers of pathogenesis in addition to blocking infection altogether.”

SARS-CoV-2 protein caught severing critical immunity pathway

This image shows the SARS-CoV-2 virus's main protease, Mpro, and two strands of a human protein, called NEMO. One NEMO strand (blue) has been cut by Mpro, and the other NEMO strand (red) is in the process of being cut by Mpro. Without NEMO, an immune system is slower to respond to increasing viral loads or new infections. Seeing how Mpro attacks NEMO at the molecular level could inspire new therapeutic approaches. 
Illustration Credit: Greg Stewart/SLAC National Accelerator Laboratory

Over the past two years, scientists have studied the SARS-CoV-2 virus in great detail, laying the foundation for developing COVID-19 vaccines and antiviral treatments. Now, for the first time, scientists at the Department of Energy’s SLAC National Accelerator Laboratory have seen one of the virus’s most critical interactions, which could help researchers develop more precise treatments.

The team caught the moment when a virus protein, called Mpro, cuts a protective protein, known as NEMO, in an infected person. Without NEMO, an immune system is slower to respond to increasing viral loads or new infections. Seeing how Mpro attacks NEMO at the molecular level could inspire new therapeutic approaches.

To see how Mpro cuts NEMO, researchers funneled powerful X-rays from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) onto crystallized samples of the protein complex. The X-rays struck the protein samples, revealing what Mpro looks like when it dismantles NEMO’s primary function of helping our immune system communicate.

New findings on how to avert excessive weight loss from COVID-19

Professor Yihai Cao.
Photo Credit: Dr. Muyi Yang.

Losing too much weight when infected with COVID-19 has been linked to worse outcomes. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process by using an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID-19 associated weight loss by targeting the blood vessels in the fat tissues,” says Yihai Cao, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and the study’s corresponding author.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Corona vaccination also protects people infected with HIV

They represent the study team: Clara Bessen, Carlos Plaza Sirvent, Adriane Skaletz-Rorowski, Anja Potthoff and Agit Simsek (from left).
Photo Credit: RUB, Marquard

A study shows that booster vaccination is particularly useful.

HIV-infected people who receive antiretroviral therapy form antibodies against Sars-Cov-2 after the Corona vaccination with mRNA vaccines. However, your immune response to vaccination is less strong than that of healthy people. The difference is reduced by a third vaccination. These results were achieved by a study with a total of 91 participants, which was carried out by a research team led by Prof. Dr. Ingo Schmitz, head of the Molecular Immunology Department at the Ruhr University in Bochum. The researchers report in the journal Frontiers in Immunology.

Vaccination protection for acquired immunodeficiency

Studies have shown that Sars-Cov-2 vaccines protect otherwise healthy people well against a severe course of Covid-19. It has so far been unclear whether this will also be the case for people with acquired immune deficiency. The research team led by Ingo Schmitz and Dr. Anja Potthoff from the Walk in Ruhr (WIR) Center for Sexual Health and Medicine at the RUB University Hospital included 71 people in her study who are HIV positive and receive antiretroviral therapy. 20 HIV-negative control persons also participated. After the first, second and third vaccinations with the mRNA vaccine from Biontech / Pfizer, they examined the immune response of the participants.

Common medicine can stop the transmission of HIV infection from mother to child

The risk of transmission of HIV infection from mother to child has been reduced in resource-poor countries.
Photo Credit: Antony Trivet

Antiviral drugs almost completely reduce the risk of mothers passing on HIV infection to their children, even in a low-income country with a high HIV incidence such as Tanzania, according to a new study in The Lancet HIV by researchers from Karolinska Institutet. The discovery raises hopes of achieving the World Health Organization’s goal of eliminating the spread of infection from mother to child.

Only 159 infants were infected

The women were followed for 18 months after giving birth when most of them had stopped breastfeeding. When the researchers examined the mothers’ children, they discovered that only 159 of the more than 13,000 infants had been infected with HIV by the age of 1.5 years. Taking into account the margin of error, this means a risk of 1.4 per cent.

New Virus Discovered in Swiss Ticks

Ticks in Switzerland carry a new pathogen: the so-called Alongshan virus. 
Photo Credit: Erik Karits

The Alongshan virus was discovered in China only five years ago. Now researchers at the University of Zurich have found the novel virus for the first time in Swiss ticks. It appears to be at least as widespread as the tickborne encephalitis virus and causes similar symptoms. The UZH team is working on a diagnostic test to assess the epidemiological situation.

Ticks can transmit many different pathogens such as viruses, bacteria, and parasites. Of particular concern are the tickborne encephalitis virus (TBEV), which can cause inflammation of the brain and of the linings of the brain and spinal cord, and bacteria leading to the infectious Lyme disease (borreliosis). The list of pathogens transmitted by ticks continues to increase, also in Switzerland: researchers from the Institute of Virology at the University of Zurich (UZH) have now detected the Alongshan virus (ALSV) for the first time in ticks in Switzerland.

Experimental COVID-19 Vaccine Offers Long-Term Protection Against Severe Disease

A study involving rhesus macaques at the California National Primate Research Center shows that COVID-19 vaccines given to infant animals protect against lung disease one year after vaccination.
 Photo Credit: CNPRC

Two-dose vaccines provide protection against lung disease in rhesus macaques one year after they were vaccinated as infants, a new study shows. The work, published in Science Translational Medicine Dec. 1, is a follow-up to a 2021 studying showing that the Moderna mRNA vaccine and a protein-based vaccine candidate containing an adjuvant, a substance that enhances immune responses, elicited durable neutralizing antibody responses to SARS-CoV-2 during infancy in preclinical research.

The co-senior authors of the paper are Kristina De Paris, professor of microbiology and immunology at the University of North Carolina at Chapel Hill; Sallie Permar, professor and chair of the Department of Pediatrics at Weill Cornell Medicine; and Koen K.A. Van Rompay, leader of the Infectious Disease Unit at the California National Primate Research at the University of California, Davis. Co-first authors are Emma C. Milligan at the Children’s Research Institute, UNC School of Medicine; and Katherine Olstad at the CNPRC.

To evaluate SARS-CoV-2 infant vaccination, the researchers immunized two groups of eight infant rhesus macaques at the CNPRC at 2 months of age and again four weeks later. Each animal received one of two vaccine types: a preclinical version of the Moderna mRNA vaccine or a vaccine combining a protein developed by the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), with a potent adjuvant formulation. Consisting of 3M’s molecular adjuvant 3M-052 formulated in a squalene emulsion by the Access to Advanced Health Institute (AAHI), the adjuvant formulation stimulates immune responses by engaging receptors on immune cells.

Researchers Develop Strategy to Thermally Stabilize Microneedle Vaccine Technology

Visual of the researcher's microneedle vaccine technology concept.
Illustration Credit: Thahn Nguyen

Researchers use sugar molecules to help eliminate the need for cold-chain storage, a common logistical hurdle for vaccine distribution

Researchers in the Department of Biomedical Engineering —a shared department between the UConn Schools of Dental Medicine, Medicine, and Engineering—unlocked a new strategy using sugar molecules to thermally stabilize their existing microneedle vaccine technology, eliminating the need for cold-chain storage.

Associate Professor Thanh Duc Nguyen from the Departments of Mechanical Engineering and Biomedical Engineering in the School of Engineering, reported this new development in a recent issue of Advanced Materials Technology. The work was led by Dr. Khanh Tran, Nguyen’s former UConn Ph.D. student currently at the Massachusetts Institute of Technology, and Dr. Tyler Gavitt, former UConn Ph.D. student currently at Duke University. Gavitt was a student of Associate Professor Steven Szczepanek in the Department of Pathobiology and Veterinary Science in the College of Agriculture, Health, and Natural Resources at UConn.

Typically, vaccinations against infectious diseases like COVID-19 require multiple painful, expensive and inconvenient injections, including a prime and several booster shots. The UConn researcher’s technology creates a self-administered microneedle patch which could be self-administered and only requires a single-time administration into skin—similar to a nicotine patch—to perform a release profile of vaccines, simulating the effect of multiple injections.