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Patients will be asked if their genetic sequence can be added to a database — shared with a pharmaceutical company — in a quest to cure a multitude of diseases.The Mount Sinai Health System began an effort this week to build a vast database of patient genetic information that can be studied by researchers — and by a large pharmaceutical company.The goal is to search for treatments for illnesses ranging from schizophrenia to kidney disease, but the effort to gather genetic information for many patients, collected during routine blood draws, could also raise privacy concerns.The data will be rendered anonymous, and Mount Sinai said it had no intention of sharing it with anyone other than researchers. But consumer or genealogical databases full of genetic information, such as Ancestry.com and GEDmatch, have been used by detectives searching for genetic clues that might help them solve old crimes.Vast sets of genetic sequences can unlock new insights into many diseases and also pave the way for new treatments, researchers at Mount Sinai say. But the only way to compile those research databases is to first convince huge numbers of people to agree to have their genomes sequenced.Beyond chasing the next breakthrough drug, researchers hope the database, when paired with patient medical records, will provide new insights into how the interplay between genetic and socio-economic factors — such as poverty or exposure to air pollution — can affect people’s health.“This is really transformative,” said Alexander Charney, a professor at the Icahn School of Medicine at Mount Sinai, who is overseeing the project.The health system hopes to eventually amass a database of genetic sequences for 1 million patients, which would mean the inclusion of roughly one out of every 10 New York City residents. The effort began this week, a hospital spokeswoman, Karin Eskenazi, said.This is not Mount Sinai’s first attempt to build a genetics database. For some 15 years, Mount Sinai has been slowly building a bank of biological samples, or biobank, called BioMe, with about 50,000 DNA sequences so far. However, researchers have been frustrated at the slow pace, which they attribute to the cumbersome process they use to gain consent and enroll patients: multiple surveys, and a lengthy one-on-one discussion with a Mount Sinai employee that sometimes runs 20 minutes, according to Dr. Girish Nadkarni of Mount Sinai, who is leading the project along with Dr. Charney.Most of that consent process is going by the wayside. Mount Sinai has jettisoned the health surveys and boiled down the procedure to watching a short video and providing a signature. This week it began trying to enroll most patients who were receiving blood tests as part of their routine care.A number of large biobank programs already exist across the country. But the one that Mount Sinai Health System is seeking to build would be the first large-scale one to draw participants primarily from New York City. The program could well mark a shift in how many New Yorkers think about their genetic information, from something private or unknown to something they’ve donated to research.The project will involve sequencing a huge number of DNA samples, an undertaking that could cost tens or even hundreds of millions of dollars. To avoid that cost, Mount Sinai has partnered with Regeneron, a large pharmaceutical company, that will do the actual sequencing work. In return, the company will gain access to the genetic sequences and partial medical records of each participant, according to Mount Sinai doctors leading the program. Mount Sinai also intends to share data with other researchers as well.Though Mount Sinai researchers have access to anonymized electronic health records of each patient who participates, the data shared with Regeneron will be more limited, according to Mount Sinai. The company may access diagnoses, lab reports and vital signs.When paired with health records, large genetic datasets can help researchers search out rare mutations that either have a strong association with a certain disease, or may protect against it.It remains to be seen if Mount Sinai, among the city’s largest hospital systems, can reach its target of enrolling a million patients in the program, which the hospital is calling the “‘Mount Sinai Million Health Discoveries Program.” If it does, the resulting database will be among the largest in the country, alongside one run by the U.S. Department of Veterans Affairs as well as a project run by the National Institutes of Health that has the goal of eventually enrolling 1 million Americans, though it is currently far short.(Those two government projects involve whole-genome sequencing, which reveal an individual’s complete DNA makeup; the Mount Sinai project will sequence about 1 percent of each individual’s genome, called the exome.)A health system in northeast Pennsylvania, Geisinger Health System, has also built a database of more than 185,000 DNA sequences, through a partnership with Regeneron. That database played a role in the discovery of mutations that can protect against obesity and fatty liver disease.Mt. Sinai Health System, in partnership with a pharmaceutical company, is planning to build a massive database of patient genetic information to be used in research.Spencer Platt/Getty ImagesRegeneron, which in recent years became widely known for its effective monoclonal antibody treatment for Covid-19, has sequenced and studied the DNA of approximately 2 million “patient volunteers,” mainly through collaborations with health systems and a large biobank in Britain, according to the company.But the number of patients Mount Sinai hopes to enroll — coupled with their racial and ethnic diversity, and that of New York City generally — would set it apart from most existing databases.“The scale and the type of discoveries we’ll all be able to make is quite different than what’s possible up until today with smaller studies,” said Dr. Aris Baras, a senior vice president at Regeneron.People of European ancestry are typically overrepresented in genomic datasets, which means, for example, that genetic tests people get for cancer risk are far more attuned to genetic variants that are common among white cancer patients, Dr. Baras said.“If you’re not of European ancestry, there is less information about variants and genes and you’re not going to get as good a genetic test as a result of that,” Dr. Baras said.Mount Sinai Health System, which has seven hospitals in New York City, sees about 1.1 million individual patients a year and handles more than 3 million outpatient visits to doctor’s offices. Dr. Charney estimated that the hospital system was drawing the blood of at least 300,000 patients annually, and he expected many of them to consent to having their blood used for genetic research.The enrollment rate for such data collection is usually high — around 80 percent, he said. “So the math checks out. We should be able to get to a million.”Mark Gerstein, a professor of Biomedical Informatics at Yale University, said there was no question that genomic datasets were driving great medical discoveries. But he said he still would not participate in one himself, and he urged people to consider whether adding their DNA to a database might someday affect their grandchildren.“I tend to be a worrier,” he said.Our collective knowledge of mutations and what illnesses they are associated with — whether Alzheimer’s or schizophrenia — would only increase in the years ahead, he said. “If the datasets leaked some day, the information might be used to discriminate against the children or grandchildren of current participants,” Dr. Gerstein said. They might be teased or denied insurance, he added.He noted that even if the data was anonymous and secure today, that could change. “Securing the information over long periods of time gets much harder,” he said, noting that Regeneron might not even exist in 50 years. “The risk of the data being hacked over such a long period of time becomes magnified,” he said.Other doctors urged participation, noting genetic research offered great hope for developing treatments for a range of maladies. Dr. Charney, who will oversee the effort to amass a million sequences, studies schizophrenia. He has used Mount Sinai’s existing database to search for a particular gene variant associated with psychotic illness.Of the three patients in the existing Mount Sinai BioMe database with that variant, only one had a severe lifelong psychotic illness. “What is it about the genomes of these other two people that somehow protected them, or maybe it’s their environment that protected them?” he asked.His team has begun calling those patients in for additional research. The plan is to take samples of their cells and use gene-editing technology to study the effect of various changes to this particular genetic variant. “Essentially what we’re saying is: ‘what is schizophrenia in a dish?’” Trying to answer that question, Dr. Charney said, “can help you hone in on what is the actual disease process.”Wilbert Gibson, 65, is enrolled in Mount Sinai’s existing genetic database. Healthy until he reached 60, his heart began to fail rapidly, but doctors initially struggled with a diagnosis. At Mount Sinai, he discovered that he suffered from cardiac amyloidosis, in which protein builds up in the heart, reducing its ability to pump blood.He received a heart transplant. When he was asked if he would share his genome to help research, he was happy to oblige. He was included in genetics research that helped identify a gene variant in people of African descent linked to heart disease. Participating in medical research was the easiest decision he faced at the time.“When you’re in the situation I’m in and find your heart is failing, and everything is happening so fast, you go and do it,” he said in an interview in which he credited the doctors at Mount Sinai with saving his life.

When surgeons remove patients’ kidney stones, they typically leave behind small stones that appear not to be causing problems.
A new randomized controlled study showed, however, that leaving these asymptomatic stones behind significantly increases the risk of a patient’s relapse in the following five years. The findings were published today in the New England Journal of Medicine.
Generally, stones under 6mm in diameter that are not a procedure’s primary target are not removed but monitored because “secondary” stones have high rates of successful passage if they move into the ureter, said lead author Dr. Mathew Sorensen, a urologist at the University of Washington School of Medicine.
“Before this study, the clinical views were pretty mixed on whether some of these stones should be treated,” he said. “Most clinicians would decide, based on the size of the stone, whether it hit the bar for treatment, and if it did not, you would often ignore the little stones.”
The investigators studied the 75 patients who were treated at multiple institutions over a span from 2015 to 2021. About half of the patients had only their large primary stone treated, while the others had primary and secondary stones removed. Relapse was defined as having to go to the emergency room or undergo an additional procedure due to a recurrence or if a follow-up CT scan showed that the secondary stones grew.
Removal of the secondary stones reduced the relapse rate by 82%, the researchers found, leading the authors to recommend that smaller stones should not be left behind.
“Results of our trial support the removal of small asymptomatic renal stones at the time of surgery with a larger stone,” their paper concluded. The authors noted that while removal of smaller stones could add to the procedure’s duration and cost, those costs would likely be less than those associated with a patient’s repeat procedure or visit to the emergency room. Some patients in the study visited the emergency department multiple times and then required surgery, the report noted.
Sorensen said he would share the study results with colleagues with the hope of changing their sensibility toward smaller stones. Further study is needed to determine whether treatment of small stones alone is justified, as technology improves and the costs and risks of intervention diminish, he said.
“I think we have proven through this rigorous study that removal of the small asymptomatic stones is beneficial when feasible and in patients that are candidates to have all their stones treated in one procedure,” he noted. “Leaving the stones behind risk trouble in the future.”
The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases and the Veterans Affairs Puget Sound Health Care System.
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Materials provided by University of Washington School of Medicine/UW Medicine. Note: Content may be edited for style and length.

Air travel can carry many risks for people with disabilities, one of which is the loss or damage of wheelchairs. According to the Air Travel Consumer Report, how many wheelchairs or scooters were lost, damaged, delayed or stolen on the country’s largest airlines in 2021?

Heart attacks and strokes are a leading cause of death in the United States, but scientists are still working to understand one of their primary triggers. What causes plaque buildup within arteries to become unstable, leading parts to suddenly burst or break away?
A key obstacle is that researchers haven’t been able to study plaques during a stroke.
For the first time, researchers at Tulane University and Ochsner Health were able to genetically sequence carotid plaque tissue collected from patients within days after a stroke. When compared to stable plaque, researchers discovered the tissues from recent stroke victims contained messenger RNA that can cause inflammation and processes that degrade a key portion of the plaque that protects against rupture, according to results recently published in Scientific Reports.
The discovery could help researchers develop new tools to stop strokes from happening.
“The genes identified in our study could be used as targets to develop new drugs or diagnostics to help prevent strokes and heart attacks,” said study senior author Cooper Woods, PhD, associate professor of physiology and medicine at Tulane University School of Medicine.
The study was co-authored by Dr. Hernan Bazan, the John Ochsner Endowed Professor for Cardiovascular Innovation at Ochsner Health.
Surprisingly, the researchers found that ruptured plaques had increased markers of B-cells, a white blood cell whose role in plaque rupture has not previously been appreciated.
Previous studies have relied on carotid artery samples obtained after the patient’s death or months after the stroke or heart attack. This either limits the information that can be obtained or misses events that occur only at the time of rupture.
Carotid artery blockage is a common cause of some ischemic strokes, which happens when the blood supply to part of the brain is interrupted, preventing brain tissue from getting necessary oxygen and nutrients. Because the mechanisms that lead to some strokes and most heart attacks involve the same plaque rupture events, these findings also have implications for heart disease.
“Inflammation is a known risk factor in atherosclerosis, leading to stroke and heart attacks,” Bazan said. “Carotid and coronary plaques develop a protective cap that, for unclear reasons, thins, making strokes and heart attacks more likely.”
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Materials provided by Tulane University. Original written by Keith Brannon. Note: Content may be edited for style and length.

Researchers in the Biomedical Engineering Department at UConn have developed a new cardiac cell-derived platform that closely mimics the human heart, unlocking potential for more thorough preclinical drug development and testing, and model for cardiac diseases.
The research, published in Cell Reports by Assistant Professor Kshitiz in collaboration with Dr. Junaid Afzal in the cardiology department at the University of California San Francisco, presents a method that accelerates maturation of human cardiac cells towards a state suitable enough to be a surrogate for preclinical drug testing.
“There is a very strong need to create human cardiac constructs for all sorts of applications. Small animal models just do not recapitulate human heart biology, and human samples are scarce,” says Kshitiz. “This matters because all drugs need to be tested for their toxicity to heart. It is widely believed that a large number of them unnecessarily fail clinical trials because we do not have human samples to test them with.”
Kshitiz and Afzal first identified the need to create a matured human cardiac tissue during their time together at Johns Hopkins Medicine.
“When methods were developed to differentiate human pluripotent stem cells to cardiac cells, it created a big hope that finally we will have human heart constructs to work with,” said Afzal. “While it is straightforward to get human cardiac cells, they are similar to fetal cells. What we need is adult cells.”
Cardiovascular safety is the number one cause for failure of preclinical drug development, and there is a long standing need to create human cardiac tissue models to test drugs for cardiotoxicity. Currently, the small animal heart models display vastly different biochemical, physiological, and genetic features from humans — making it difficult to replicate the human heart in preclinical studies. In particular, it is very difficult to perform metabolic assessment of current cardiac constructs. Heart beats continuously and is a highly metabolically active organ.
“Metabolic and redox maturation is critical for heart cells, and we are able to achieve it and possibly create a gold standard — fundamentally shifting our expectations of creating a metabolically mature cardiac tissue,” the researchers said.
In the study, the researchers utilized the cardiac biology in an adult human heart to rapidly mature differentiated cardiac cells into a more adult-like state. Within 30 days, the researchers achieved cardiac cells that displayed structural, mechanical, metabolic, and electrophysiological characteristics close to adult heart muscle.
The researchers are optimistic that this application will not only be used for preclinical drug testing, but can also be used in future precision disease modeling to study disease mechanisms and test for regenerative therapies. The researchers hope that the many drugs that fail unnecessarily due to non-human methods will be salvaged for cures for cancer, immune and neurological diseases.
UConn Health researchers Yamin Liu, Wenquang Du, Yasir Suhail, Pengyu Zong, Jianlin Feng, Visar Ajeti, Maya Yankova, Alix Deymier, and Lixia Yue also contributed to this study.
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Materials provided by University of Connecticut. Original written by Courtney Chandler. Note: Content may be edited for style and length.

Men and women with monkeypox share their stories on social media, to fight stigma and demand more action.When Matt Ford, 30, an actor in Los Angeles, tested positive for monkeypox in June, he posted videos on Twitter and TikTok to show what it was like.Wearing a gray T-shirt and staring directly into the camera, he offered viewers close-ups of the “gross spots” all over his body, including his face, arms, belly. He also mentioned “some in my more sensitive areas, which also tend to be the most painful.”“So painful, I had to go to my doctor and get painkillers just to be able to go to sleep,” he added, before listing other symptoms: sore throat, cough, fever, chills, night sweats, swollen lymph notes.In a time when people often use social media to showcase idealized versions of themselves, displaying one’s warts — or in Mr. Ford’s case, several of the “more than 25” dark lesions on his body — was perhaps unusual.“The reason I’m speaking out,” he said in the video, “is mainly because it’s one thing to know there’s a monkeypox outbreak happening, but it’s another to know exactly what it means for someone’s body and particularly what it means if it happens to a friend or to you.”Silver Steele, 42, an adult film actor in Houston, used Twitter to share his highly graphic and personal monkeypox diary, including an intimate selfie in July that showed eight blueberry-size sores clustered under his lips.Also in July, Camille Seaton, 20, a gas station cashier in Smyrna, Ga., racked up more than 10 million views in a series of TikTok posts that detailed her bout with monkeypox. One of them started with Ms. Seaton covering her mouth with a hand as she said, “Trigger warning.” Then she revealed the lower part of her face covered with nearly a dozen sores.Viewers have responded with heart emojis and thank you’s, but reactions have not always been sympathetic. Conspiracy theories abound.Camille Seaton, a gas station attendant from Georgia, shared her monkeypox journey on TikTok.Photo courtesy of Camille SeatonPhoto courtesy of Camille SeatonJeffrey Todd, 44, a casting director in Los Angeles, went public with his monkeypox diagnosis in late July, including a video in which he removed a bandage from his face to reveal a purplish lesion. One commenter accused him of being an actor hired to shill for Pfizer.Never mind that Tpoxx, the only drug that is being prescribed to treat monkeypox, is manufactured by Siga Technologies. (The drug, which is only approved for smallpox, is being used off-label, and only sparingly.) Mr. Todd said that his video was taken down momentarily by TikTok, but was restored when he made another video addressing the haters.In certain ways, these videos recall the early days of AIDS, when women like Elizabeth Glaser and Alison Gertz joined the activist Larry Kramer and the artist Keith Haring as prominent spokespeople for those living with H.I.V.What to Know About the Monkeypox VirusCard 1 of 7What to Know About the Monkeypox VirusWhat is monkeypox?

Insects are the world’s smallest flying migrants, but they can maintain perfectly straight flight paths even in unfavorable wind conditions, according to a new study from the Max Planck Institute of Animal Behavior (MPI-AB) and the University of Konstanz. Researchers radio tracked migrating hawkmoths for up to 80 kilometers—the longest distance that any insect has been continuously monitored in the wild. By closely following individuals during migration, the world-first study unlocks a century-old mystery of what insects do over their long-range journeys. The study, published in Science, confirms that hawkmoths can accurately maintain straight trajectories over long distances, employing sophisticated strategies to counter and correct for unfavorable wind conditions. The findings reveal that insects are capable of accurate navigation, confirming that an internal compass guides them on their long journeys.
With trillions of individuals migrating every year, insects are some of the most common migrating animals on Earth. They include species of renown, such as the monarch butterfly, as well as species of enormous societal and environmental importance, such as locusts, mosquitos, and bees. But even though insect migrants far outnumber better-known migrants, such as birds or mammals, their migration is the least understood form of long-range animal movement.
The problem, for the most part, has been methodological. “Studying insects on the move is a formidable challenge,” says first author Myles Menz, who conducted the research at MPI-AB and is now a lecturer at James Cook University in Australia. “They’re usually too numerous to mark and find again, and too small to carry tracking devices.”
Much of what we know about insect migration has come from studies that sample insects at a single moment in time, such as through radar or direct observation, which has left vast blank spots in our knowledge. “Understanding what insects do during migration, and how they respond to weather, is a last frontier in migration science,” says Menz.
The current study, which followed radio-tagged individuals in a light aircraft, is the first to continuously study nocturnal migrating insects in the wild and represents the longest distance over which any insect has been continuously tracked in the field. The team, which includes researchers from the MPI-AB and University of Konstanz in Germany and the University of Exeter in the UK, focused on the death’s-head hawkmoth—a large, nocturnal migrant that travels up to 4000 kilometers between Europe and Africa every year. Like many insects, the species is a multi-generational migrant, which means that no individual knows the entire route.
At the MPI-AB in Konstanz, Germany, the team reared caterpillars until adulthood in the laboratory to ensure that individuals were naïve. When moths emerged as adults, they were fixed with radio tags weighing 0.2 grams—less than 15% of adults’ body weight. “The moths would probably eat more weight than that in a night, so these tags are extremely light for the insects,” says Menz.
The researchers released the tagged moths and waited for flight to begin, after which they chose a single individual to follow at a time. The team followed 14 moths each for up to 80 kilometers or 4 hours—a stretch long enough to be considered migratory flight—using antennas mounted on a Cessna airplane to detect precise locations every five to 15 minutes. Insects were followed in the south-south-west direction from Konstanz into the Alps, which follows the route taken by hawkmoths towards the Mediterranean and Northwest Africa.
Due to practical constraints of flying in an aircraft, the scientists tracked moths continuously until the insects stopped on route. “When you’re in an airplane, it becomes extremely difficult to wait for the insects to begin migrating again because you would have to be in the air when this happens, which could be anytime in the night,” says senior author Martin Wikelski, a movement ecologist from the MPI-AB and University of Konstanz, who piloted the plane during the study.
The results show that moths maintained perfectly straight trajectories for long distances during flight. This was not because they waited for favorable tailwinds. Rather, they employed a range of flight strategies to buffer against prevailing winds, allowing them to hold their course throughout the night. When winds were favorable, they flew high and slow, allowing the air to carry them. But during harsh headwinds or cross winds, they flew low to the ground and increased speed to keep control of their path.
Says Menz: “For years it was assumed that insect migration was mostly about getting blown around. But we show that insects are capable of being great navigators, on par with birds, and are far less vulnerable to wind conditions than we thought.”
“By showing that it is technically possible to continuously monitor individual insects over migration, and to observe their flight behavior in detail, we hope to inspire more studies to answer many more big questions in this area.”
For the study authors, the next step is to answer the question of how moths are able to maintain such straight lines. “Based on past lab work, it’s possible that the insects are using internal compasses, both visual and magnetic, to chart their way around the world,” says Menz.

An ongoing debate among scientists, on why chimpanzees and other nonhuman primates cannot speak or sing like humans, has focused mainly on evolutionary changes in human brain development. Attention has now expanded to anatomical changes of the voice box that may have played a role in our capacity to produce complex sounds.
A team of researchers from Japan and Europe has now revealed that evolution of the human larynx contributed to the stable voices we use to communicate. Unexpectedly, these changes do not include the addition of structures but rather the loss of specific vocal folds or cords in the larynx.
“Paradoxically, the increased complexity of human communication involved a simplification of our vocal anatomy,” says lead author Takeshi Nishimura of KyotoU’s Center for the Evolutionary Origins of Human Behavior, or EHUB.
Most primates have thin, ribbon-like vocal membranes rising out of their vocal folds. The loss of these air sacs seen in chimpanzees and other apes seems to have provided a stable voice quality and controllable voice pitch that we humans use when singing or speaking.
Nishimura adds, “Studies by the late Dr Sugio Hayama, on which our work was largely based, showed that evolutionary modifications in the larynx were necessary for the evolution of spoken language. We took his work to the next level, demonstrating that the simpler the vocal fold morphology, the easier it is to control its vibrations.”
Senior author Tecumseh Fitch of the University of Vienna explains that the thin vocal membranes found in the larynx in the team’s large selection of monkeys and apes are specific to nonhuman primates. Based on computer modeling showing how vocal membranes allow nonhuman primates to create their characteristic vocalizations, the team posits that the melodious quality of the human voice directly results from losing these membranes during evolution.

A joint research team from the LKS Faculty of Medicine, The University of Hong Kong (HKUMed) and City University of Hong Kong (CityU) has discovered that the electrical stimulation of the eye surface can alleviate depression-like symptoms and improve cognitive function in animal models. These significant findings were recently published in Brain Stimulation and the Annals of the New York Academy of Sciences.
Background
Major depression is the most common and severe psychiatric disorder across the world. Recently, the World Health Organization reported that the COVID-19 pandemic had triggered a massive increase in the number of people with anxiety and depression. About a quarter of patients do not respond adequately to the treatments available.
Dr Lim Lee Wei, Assistant Professor in the School of Biomedical Sciences, HKUMed and a former Lee Kuan Yew Research Fellow in Singapore, reported in 2015 that deep brain stimulation of the prefrontal cortex in the brains of animals could improve memory function and relieve depressive symptoms. These therapeutic effects were attributed to the growth of brain cells in the hippocampus, a region of the brain known to be involved in learning and memory function. However, this technique, also known as deep brain stimulation, is invasive and requires surgery to implant electrodes in the brain, which may cause side effects such as infections and other post-operative complications.
Research findings and significance
A team of Hong Kong researchers headed by Dr Lim Lee Wei; Dr Leanne Chan Lai-hang, Associate Professor in the Department of Electrical Engineering, CityU; Professor Chan Ying-shing, Dexter H C Man Family Professor in Medical Science, Professor of the School of Biomedical Sciences, Associate Dean (Development and Infrastructure), HKUMed, and Director of the Neuroscience Research Centre, HKU, have been looking for alternative ways to treat neuropsychiatric diseases. They discovered that the non-invasive stimulation of the corneal surface of the eye (known as transcorneal electrical stimulation, or TES) that activates brain pathways, resulted in remarkable antidepressant-like effects and reduced stress hormones in an animal model for depression. Furthermore, this technique induced the expression of genes involved in the development and growth of brain cells in the hippocampus.

Researchers at the AIDS Institute, The University of Hong Kong (HKU), Department of Microbiology, School of Clinical Medicine, the LKS Faculty of Medicine of The University of Hong Kong (HKUMed) and the State Key Laboratory of Emerging Infectious Diseases, HKU, together with structural biologists at The Hong Kong University of Science and Technology (HKUST), have demonstrated that ZCB11, a broadly neutralising antibody derived from a local mRNA-vaccinee against the spreading Omicron variants of SARS-CoV-2, displays potent antiviral activities against all variants of concern (VOCs), including the dominantly spreading Omicron BA.1, BA1.1 and BA.2. Critically, either prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. The research paper is now published online in Nature Communications.
Background
The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. In response to the continuous emergence of SARS-CoV-2 Omicron variants with unpredictable pathogenicity, universal masking, quarantine and endless viral testing have to be maintained, resulting in social anxiety and economic disruption. It is therefore important to investigate into whether host immune response can generate broadly neutralising antibodies, which is essential not only for antibody-based immunotherapy but also for vaccine optimisation to induce equally broad protection.
Research methods and findings
In this study, the HKUMed team has established an effective platform of cloning technology that natively pairs antibody genes from individual human memory B cells. Using this technique, the research team successfully discovered ZCB11 after screening 34 BNT162b2-vaccinees in Hong Kong, and demonstrated that ZCB11 neutralises all VOCs including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2) and Omicron (B.1.1.529) by testing both pseudoviruses and authentic live viruses. Importantly, ZCB11 administration protects lung infection against both live Omicron and Delta viral challenges in golden Syrian hamsters respectively, under both prophylactic and therapeutic conditions. Furthermore, the HKUST collaborative team deciphered the complex structure of ZCB11 and spike protein at atomic resolution using single particle cryo-EM, revealing the unique molecular mode of ZCB11 action, which lays a solid foundation for upcoming structure-guided antibody and vaccine optimisation.
Significance of the study
‘The findings suggested that ZCB11 is a promising antibody drug for biomedical interventions against pandemic SARS-CoV-2 variants of concern,’ remarked Professor Chen Zhiwei, Director of AIDS Institute and Professor of the Department of Microbiology, School of Clinical Medicine, HKUMed, who led the study. ‘Although our findings implicate that the HKUMed team is at the world’s forefront of research and development of human antibody drugs and vaccines against COVID-19, we still urgently need to establish large-scale manufacturing capacity and clinical translational hubs in Hong Kong, in order to meet its aspiration of becoming an international innovation centre.’