The antibodies target portions of the SARS-CoV-2 spike protein that resist mutation, potentially leading to better treatments and vaccines
One challenge in the battle against COVID-19 is the emergence of SARS-CoV-2 variants, especially the Delta variant, which may be more resistant to neutralizing antibodies compared with the original coronavirus. But now, scientists led by researchers at the Fred Hutchinson Cancer Research Center (Fred Hutch) in Seattle say they have identified antibodies that could be broadly protective against multiple sarbecoviruses, the subgenus that contains SARS-CoV-2 as well as SARS-CoV-1, the virus responsible for the 2002-2004 severe acute respiratory syndrome (SARS) outbreak.
In “SARS-CoV-2 RBD Antibodies That Maximize Breadth and Resistance to Escape,” the researchers described how they compared 12 antibodies obtained from patients infected with either SARS-CoV-2 or SARS-CoV-1. They pointed to one antibody in particular—S2H97—that could lead to development of new vaccines and therapies against current and future variants. It might even protect against sarbecoviruses that have not yet been identified, they wrote.
Unsaid in the news release about these research findings is the fact that these particular antibodies could eventually become useful biomarkers for clinical laboratory tests designed to help physicians determine which patients have these antibodies—and the protection from infection they represent—and which do not.
So far, however, S2H97 has only been tested in hamsters. But results are promising.
“This antibody, which binds to a previously unknown site on the coronavirus spike protein, appears to neutralize all known sarbecoviruses—the genus of coronaviruses that cause respiratory infections in mammals,” said Jay Nix, PhD, an affiliate in Berkeley Lab’s Biosciences Area and Beamline Director of the Molecular Biology Consortium at Berkeley Lab’s Advanced Light Source (ALS), in a Berkeley Lab news release. “And, due to the unique binding site on mutation-resistant part of the virus, it may well be more difficult for a new strain to escape,” he added.
Scientists have long known that the SARS-CoV-2 virus uses the spike protein to attach to human cells. The federal Centers for Disease Control and Prevention (CDC) notes that the variants have mutations in their spike proteins that make some of them more transmissible.
The Delta variant, the CDC notes, was the predominant variant in the US as of August 28, 2021. It “has been shown to have increased transmissibility, potential reduction in neutralization by some monoclonal antibody treatments, and reduction in neutralization by post-vaccination sera,” the agency states.
The key to S2H97, the researchers wrote, is that it targets a portion of the spike protein that is common among sarbecoviruses, and that is likely to be resistant to mutations.
The researchers used a variety of techniques to analyze how the 12 antibodies bind to the virus. They “compiled a list of thousands of mutations in the binding domains of multiple SARS-CoV-2 variants,” Nature reported. “They also catalogued mutations in the binding domain on dozens of SARS-CoV-2-like coronaviruses that belong to a group called the sarbecoviruses. Finally, they assessed how all these mutations affect the 12 antibodies’ ability to stick to the binding domain.”
William Schaffner, MD (above), Professor of Preventive Medicine in the Department of Health Policy as well as Professor of Medicine in the Division of Infectious Diseases at the Vanderbilt University School of Medicine in Nashville, believes that “people who test positive for SARS-CoV-2 and who are at risk of progressing to severe disease—including those who are over the age of 65 years and those who have weakened immune systems—should talk with a doctor about receiving monoclonal antibody treatment,” Medical News Today reported. “[The monoclonal antibody treatment is] designed to prevent the evolution of the infection from a mild infection into a serious one,” he noted. “In other words, you’ve just [contracted the virus], but we can now give you a medication that will help prevent [you] being hospitalized and getting seriously ill.” (Photo copyright: Vanderbilt University.)
Earlier Antibody Treatment Receives an EUA from the FDA
In issuing the EUA for sotrovimab, the FDA cited “an interim analysis from a phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in 583 non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. Of these patients, 291 received sotrovimab and 292 received a placebo within five days of onset of COVID-19 symptoms.”
Among these patients, 21 in the placebo group were hospitalized or died compared with three who received the therapy, an 85% reduction.
“While preventive measures, including vaccines, can reduce the total number of cases, sotrovimab is an important treatment option for those who become ill with COVID-19 and are at high risk—allowing them to avoid hospitalization or worse,” stated Adrienne E. Shapiro, MD, PhD, of the Fred Hutchinson Cancer Research Center in a GSK news release. Shapiro was an investigator in the clinical trial.
The EUA allows use of sotrovimab in patients who have tested positive for SARS-CoV-2, have mild-to-moderate symptoms, and “who are at high risk for progression to severe COVID-19, including hospitalization or death. This includes, for example, individuals who are 65 years of age and older or individuals who have certain medical conditions.” It is not authorized for patients who are hospitalized or for those who require oxygen therapy.
The therapy was originally known as VIR-7831. The companies say they have developed a similar treatment, VIR-7832, with modifications designed to enhance T cell function against the disease.
The antibody, they wrote, targets a region of the SARS-CoV-1 spike protein that is “highly conserved” among sarbecoviruses. Clinical laboratory testing, they wrote, also indicated that the therapy was likely to be effective against known SARS-CoV-2 variants.
“Our distinctive scientific approach has led to a single monoclonal antibody that, based on an interim analysis, resulted in an 85% reduction in all-cause hospitalizations or death, and has demonstrated, in vitro, that it retains activity against all known variants of concern, including the emerging variant from India,” stated Vir Biotechnology CEO George Scangos, PhD, in the GSK news release. “I believe that sotrovimab is a critical new treatment option in the fight against the current pandemic and potentially for future coronavirus outbreaks, as well.”
Pathologists and clinical laboratory managers working with rapid molecular tests and antibody tests for COVID-19 will want to monitor the development of monoclonal antibody treatments, as well as further research studies that focus on these specific antibodies.
If tattoos can accurately be used in the diagnostic process, might clinical laboratories soon offer these types of diagnostic tattoos at their patient service centers?
Could color-changing tattoos help diagnose illnesses? Researchers at the ATLAS Institute at the University of Colorado Boulder think so. They are working on prototypes of permanent tattoos that can detect chemical changes in the body and smart tattoo ink that would take the concept of wearable medical devices to a whole new level.
Called “dynamic” or “smart” tattoos, these color-changing tattoos have a biomedical purpose. They alert individuals to potential health issues due to changes in the biochemistry in their body. The technology has already been used in animal studies to detect sodium, glucose, electrolytes, and pH levels. Pathologists and clinical lab manager will recognize the value of a relatively non-invasive way to measure and track changes in these types of biomarkers.
“We developed a photochromic tattoo that serves as an intradermal ultraviolet (UV) radiometer that provides naked-eye feedback about UV exposure in real time. These small tattoos, or ‘solar freckles’, comprise dermally implanted colorimetric UV sensors in the form of nano encapsulated leuco dyes that become more blue in color with increasing UV irradiance,” the ATLAS scientists wrote.
Studies analyzing the efficacy of dynamic tattoos have provided strong evidence that they can be engineered to change color and sense and convey medical information. This field is called “dynamic tattoos” and in recent years various proof-of-concept studies have demonstrated that tattoos can be used to “pick up changes in sodium, glucose, electrolytes or pH levels in animal models,” Labroots reported.
“We demonstrate the tattoos’ functionality for both quantitative and naked-eye UV sensing in porcine skin ex vivo, as well as in human skin in vivo. Solar freckles offer an alternative and complementary approach to self-monitoring UV exposure for the sake of skin cancer prevention,” the researchers explained in their ACS Nano article.
“Activated solar freckles provide a visual reminder to protect the skin, and their color disappears rapidly upon removal of UV exposure or application of topical sunscreen. The sensors are implanted in a minimally invasive procedure that lasts only a few seconds yet remain functional for months to years,” they added.
“These semipermanent tattoos provide an early proof-of-concept for long-term intradermal sensing nanomaterials that provide users with biomedically relevant information in the form of an observable color change,” the ATLAS researchers concluded.
“When you think about what a tattoo is, it’s just a bunch of particles that sit in your skin,” Carson Bruns, PhD, Assistant Professor, Laboratory for Emergent Nanomaterials, ATLAS Institute, Mechanical Engineering, told Technology.org. “Our thought is: What if we use nanotechnology to give these particles some function?”
The invisible tattoos Bruns and the ATLAS team created turn blue in the presence of harmful levels of ultraviolet radiation to inform wearers that their skin needs protection and to apply or reapply sunscreen.
“I have always been interested in both art and science. My favorite type of art is tattooing and my favorite type of science is nanotechnology,” Carson Bruns, PhD (above), Assistant Professor, Mechanical Engineering, ATLAS Institute, told Inked. “When I had an opportunity to start a new research program, I thought it would be really fun and interesting to try and put the two together.” Might innovative medical laboratories one day operate “tattoo parlors” in their patient service centers to provide patients with tattoos that monitor key biometrics? (Photo copyright: Inked.)
The tattoo ink used for these tattoos contains a UV-activated dye inside of a plastic nano capsule that is less than a thousandth of a millimeter in size, or several sizes smaller than the width of a human hair. The capsules protect the dyes from wear and tear while allowing them to sense and respond to biochemical changes in the body. These tattoos are implanted into the skin using tattoo machines, much like getting a regular tattoo.
“I call them solar freckles because they’re like invisible freckles that are powered by sunshine,” Bruns told Inked, adding, “Millions of cases of preventable skin cancer are treated every year. I hope that the UV-sensitive tattoo will help us reduce the number of those cases by reminding people when their skin is exposed to unsafe levels of UV light.”
Dynamic Tattoos May Help People Lead Healthier Lives
One downside to these tattoos is that they only last a few months before they begin to degrade, requiring the wearer to get a “booster” tattoo.
The researchers hope that someday similar tattoo technologies will be applied to a wide variety of preventative and diagnostic applications. The goal is to enable people to detect health issues and allow them to lead healthier lives.
“We want to make tattoos that will allow you to, for example, sense things that you can’t currently sense,” Bruns told Inked. “Sometimes I joke that we want to make tattoos that give you superpowers.”
The ATLAS scientists imagine a future where tattoos can detect things like blood alcohol levels or high/low blood sugar levels or other changes in a person’s biochemistry.
“More generally, I hope that smart tattoos will help people stay healthy and more informed about their body, while also giving people new ways to express themselves creatively,” Bruns said.
Using Dynamic Tattoo to Detect Cancer
In 2018, a team of biologists created a tattoo comprised of engineered skin cells and an implantable sensor which could detect elevated blood calcium levels that are present in many types of cancers. These cancer-detecting tattoos were tested on living mice and would darken to notify researchers of potential problems.
Scientists at the Department of Biosystems Science and Engineering at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland, developed a biomedical tattoo that uses bio sensitive ink and changes color based on variations in the body’s interstitial fluid. It recognizes four widespread cancers:
breast,
colon,
lung, and
prostate.
“Nowadays, people generally go to the doctor only when the tumor begins to cause problems. Unfortunately, by that point it is often too late,” Martin Fussenegger, PhD, Professor of Biotechnology and Bioengineering at the Department of Biosystems Science and Engineering (D-BSSE) of the ETH Zurich in Basel as well as at the University of Basel, told Medical News Today.
“For example, if breast cancer is detected early, the chance of recovery is 98%,” he continued. “However, if the tumor is diagnosed too late, only one in four women has a good chance of recovery.”
Though it appears that dynamic tattoos may be a functional and decorative way to track health, rigorous research and safety testing on human subjects will be required before clinical laboratories can set up diagnostic tattoo parlors in their offices.
Nevertheless, this concept demonstrates how different technologies under development may provide clinical laboratories with innovative and unusual diagnostic tools in the future.
Latest research provides new opportunities for clinical laboratories to demonstrate how testing can help curb hospital-acquired infections
Pathologists, microbiologists, and other healthcare providers have long been aware that hospital patients taking antibiotics are at higher risk of contracting the potentially deadly Clostridium difficile infection (C. diff). But new research adds an interesting twist to this issue.
Recent research indicates that being a “second user” of a bed may be another risk factor for acquiring the disease. This will give clinical laboratory professionals, microbiologists, and others on the front lines of hospital infection control programs another factor to consider when working to halt the spread of hospital-acquired infections (HAIs).
The recent study was published online in JAMA Internal Medicine. It shows that patients put in a hospital bed previously occupied by someone given antibiotics are 22% more likely to develop the C. difficile infection, even if they do not themselves receive antibiotics. (more…)
Ohio State University study shows correlation between genetic variability among cancer cells within tumors and the survival of patients with head-and-neck cancers
Anatomic pathologists and clinical laboratories may gain a tool to identify tumor heterogeneity. This would enable them to ultimately guide personalized cancer therapies if a new method for measuring genetic variability within a tumor and predicting outcomes is confirmed in future studies.
Scientists Seek Cause of Resistance to Cancer Treatment
Pathologists likely to be surprised to learn that consumers reach objectively to the results of genetic tests
How consumers will react to the results of genetic tests is a subject of constant debate by many health policy wonks. This same debate has its counterpart in the clinical laboratory testing industry, as pathologists and PhDs discuss the pros and cons of allowing consumers to order their own predictive genetic tests and molecular diagnostic assays.
Rapid developments in whole human genome sequencing will soon make it affordable and fast for any consumer to run their entire genome and have the results analyzed and presented to them in a detailed, easy-to-understand manner. In practical terms, it means medical laboratories and anatomic pathology groups will need to be ready to respond to consumer demand for access to these tests.
