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Serosurveillance provides estimates of antibody levels against infectious diseases and is considered the gold standard for measuring population immunity due to past infection or vaccination. A study publishing November 10 in the open access journal PLOS Medicine jointly authored by the World Health Organization’s (WHO) Unity Studies and SeroTracker and colleagues suggests that based on seroprevalence, global COVID-19 infection rates are likely to be higher than previously reported.
The global scale of COVID-19 infections is not well understood. Routine surveillance data underestimates infection and cannot infer population immunity due to asymptomatic infections and uneven access to diagnostics. In order to ascertain the true rates of infection and indicators of immunity in the population against SARS-CoV-2 over time, researchers conducted a systematic review and meta-analysis of seroprevalence studies published from January 1, 2020 to May 20, 2022. From their search parameters, the authors identified 965 distinct seroprevalence studies sampling 5,346,069 participants between January 2020 and April 2022, with 43% of these studies being from low-middle income countries. They analyzed seroprevalence by country and month, estimating regional and global seroprevalence over time, and estimated seropositivity rates from infection versus infection or vaccination.
The researchers found that global seroprevalence has risen from 7.7% in June 2020 to 59.2% in September 2021, suggesting two-thirds of the global population may be SARS-CoV-2 seropositive from either vaccination or infection. Estimates of COVID-19 infections based on seroprevalence data far exceed reported cases, suggesting a bigger global impact of COVID-19 than previously known. The study did have limits, such as underrepresentation of some countries in the data, and overrepresentation of others.
According to the authors, “This study on global seroprevalence of SARS-CoV-2 antibodies found that while seroprevalence has increased over time, a third of the global population tested negative for antibodies against the virus as of September 2021 estimates. It was also found that compared to seroprevalence estimates, routine testing for COVID-19 has largely underestimated the number of global infections.”
Bergeri, Whelan, Ware, Subissi and colleagues add, “As we enter the third year of the COVID-19 pandemic, implementation of a global system or network for targeted, multi-pathogen, high-quality and standardized collaborative serosurveillance is a crucial next step to monitor the COVID-19 pandemic and contribute to preparedness for other emerging respiratory pathogens.”
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A team of researchers at The University of Texas MD Anderson Cancer Center has developed a nanotechnology platform that can change the way the immune system sees solid tumor cells, making them more receptive to immunotherapy. The preclinical findings suggest this adaptable immune conversion approach has the potential for broad application across many cancer types.
The study, published today in Nature Nanotechnology, details the use of this platform to artificially attach an activation molecule to the surface of tumor cells, triggering an immune response in both in vivo and in vitro models. Wen Jiang, M.D., Ph.D., assistant professor of Radiation Oncology, and Betty Kim, M.D., Ph.D., professor of Neurosurgery, co-led the study.
“With this new platform, we now have a strategy to convert a solid tumor, at least immunologically, to resemble a hematological tumor, which often has a much higher response rate to immunotherapy treatments,” Jiang said. “If we are able to translate and validate this approach in the clinic, it may enable us to get closer to the maximum level of activity from immunotherapy drugs with cancers that have not traditionally responded well.”
Immunotherapy has high response rates in blood cancers like leukemia and lymphoma, but success has been variable across solid tumors. Scientists have been working to further understand the mechanisms prohibiting a better response. One explanation is that varied expression of immune regulatory molecules on blood cancer versus solid tumor cells impact how they interact with immune cells.
The signaling lymphocytic activation molecule family member 7 (SLAMF7) receptor is critical in activating the body’s immune cells against cancer cells, acting as an “eat me” signal. However, it is found almost exclusively on the surface of blood cancer cells and not in solid tumor cells, making it an attractive target for the researchers’ immune conversion approach.
To promote the expression of SLAMF7 on solid tumor cells, the researchers developed their bispecific tumor-transforming nanoconjugate (BiTN) platform. These nanosystems are designed with one molecule to bind to the surface of targeted tumor cells and a second molecule to activate an immune response.
In this study, the researchers used BiTN with SLAMF7 and a HER2-recognizing antibody to target HER2-positive breast cancer cells. In laboratory models, the nanoconjugate successfully attached SLAMF7 to the breast cancer cells, resulting in phagocytosis, or ingestion, by immune cells. The approach also sensitized the breast cancer cells to treatment with an anti-CD47 antibody, which blocks the “don’t eat me” signal from tumor cells to further increase responses in solid tumors.
According to the authors, one of the most exciting things about this platform is its broad potential applications. The approach would not be specific to one cancer type or one regulatory molecule, rather it has the potential to be a universal strategy for several different solid tumor types. As a proof of concept, the authors also developed BiTN with folate instead of the anti-HER2-antibody to target triple-negative breast cancer with similar results.
“Because these are engineered constructs, this can be used as a plug-and-play approach to incorporate different tumor-targeting agents or immune molecules onto the surface of the nanoparticle,” Kim said. “For patients with solid tumors that have not responded to immunotherapy, we see this as an added advantage to target the part of the tumor that didn’t respond.”
The study was supported in part by the Susan G. Komen Foundation Career Catalyst Research Grant, the National Cancer Institute/National Institutes of Health (1K08 CA241070, P30 CA016672) and the United States Department of Defense.

Though the COVID-19 pandemic provided a brief respite, influenza virus is back in circulation and, as usual, poses a special danger to people over the age of 65. But why are older people more susceptible to the flu? New research from the U-M Medical School, published in Nature Communications, offers clues.
The study, led by first author Judy Chen, a Ph.D. candidate, senior author Daniel Goldstein, M.D., the Eliza Maria Mosher Collegiate Professor in Internal Medicine and Professor of Microbiology and Immunology, and their team investigates why cells called alveolar macrophages, the first line of defense in the lungs, appear to be compromised with age.
These macrophages are immune cells that attack invaders like the flu virus and live in the small air sacs, or alveoli, inside the lungs. Importantly, these cells appear to be lost with aging.
Previous research by another group showed that when macrophages from an old mouse were put into a young mouse, and cells looked young again. “This drove us to believe that something in the environment of the lungs is contributing to this,” said Chen.
Signs pointed to a lipid immune modulator known as prostaglandin E2 (PGE2) with wide ranging effects, from labor induction in pregnancy to inflammation with arthritis. The study team discovered there is more PGE2 in the lungs with age. This increase in PGE2, Chen explained, acts on the macrophages in the lung, limiting their overall health and ability to generate.
The team suspects that the buildup of PGE2 is yet another marker of a biological process called senescence, which is often seen with age. Senescence serves as insurance against the runaway division of damaged cells; cells that are senescent are no longer able to replicate.
“One of the interesting things about these cells is they secrete a lot of inflammatory factors,” said Chen.
The study showed that with age, the cells lining the air sacs in the lungs become senescent, and these cells lead to increased production of PGE2 and suppression of the immune response.
To test the link between PGE2 and increased susceptibility to influenza, they treated older mice with a drug that blocks a PGE2 receptor. “The old mice that got that drug actually ended up having more alveolar macrophages and had better survival from influenza infection than older mice that did not get the drug,” said Chen.
The team plans to next investigate the various ways PGE2 affects lung macrophages as well as its potential role in inflammation throughout the body. “As we get older, we become more susceptible not only to influenza, but to other infections, cancers, autoimmune diseases as well.”
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Materials provided by Michigan Medicine – University of Michigan. Original written by Kelly Malcom. Note: Content may be edited for style and length.

Testing whether a new drug impacts the progression of Parkinson’s disease takes years, in part because the disease often advances so slowly. Many Parkinson’s patients don’t have any worsening of their symptoms over the course of a typical clinical trial, even without treatment.
Now, Scripps Research scientists have developed a tool that analyzes Parkinson’s disease patients’ genetic and clinical data to predict who is most likely to rapidly progress. The approach, described in npj Parkinson’s Disease, will let clinical researchers select the most at-risk patients and design shorter, more powerful trials to assess Parkinson’s drugs, they say.
“If clinicians are able to enroll in trials only those patients predicted to progress, they can get much faster results and move this field along more quickly,” says senior author Ali Torkamani, PhD, professor and director of Genomics and Genome Informatics at the Scripps Research Translational Institute.
Parkinson’s disease is a progressive disorder of the nervous system and affects about one million people in the United States. The earliest symptoms are often barely noticeable tremors, and over the course of many years the disease progresses, eventually impacting movement, posture, facial expressions, speech and eating, as well as causing pain and dementia. However, the order and speed at which these symptoms worsen varies greatly between people. Over a single year, for instance, many patients won’t get worse, making it difficult and time-consuming to study the effectiveness of drugs at slowing this progression.
Torkamani, along with Scripps Research colleagues and collaborators at Takeda — who are developing investigational Parkinson’s Disease treatments — set out to better predict this short-term progression in patients considered for inclusion in clinical studies to slow down this disease. They analyzed the progression over 12, 24 and 36 months of patients enrolled in two existing cohorts — the Parkinson’s Progression Markers Initiative and the Parkinson’s Disease Biomarkers Program. In all, the team used data including genetics, clinical exam information, brain scans and treatments, on 879 patients.
Overall, 529 patients were found to be “progressors” over the first 12 months of the study, with their symptoms significantly worsening, while 350 were grouped as “non-progressors.” Torkamani’s group used a machine learning approach to develop a model that could predict, with 77% accuracy, which group patients belonged to.
“This model worked by combining different aspects of comprehensive disease profiling,” says Torkamani. “Genetic risk factors were the most powerful predictor, but other factors were important to include as well.”
Some of the strongest signals, he says, included whether a patient had a mutation in LRRK2 — this known risk factor for Parkinson’s disease makes patients more likely to develop early onset disease, but then their symptoms progress more slowly.
For now, the model doesn’t have clinical value for individual patients, since there are no drugs that have been shown to slow the progression of Parkinson’s. However, the researchers hope that being able to choose “progressors” for clinical trials makes it easier and faster to pinpoint these kinds of drugs as the field moves forward.
“Right now, these clinical trials are large and tend to take two to three years,” says Torkamani. “We’re hoping to empower smaller trials that are on the order of a one-year time frame.”
The Scripps Research scientists also plan to expand their model to try to predict other aspects of Parkinson’s. For instance, can genetic markers predict which Parkinson’s patients will develop psychosis or depression? The same approach they took in the current study — integrating clinical and genetic information — could also be useful in analyzing the progression of other neurodevelopmental disorders.
This work was supported by funding from Takeda Development Center Americas, Inc., and the National Institutes of Health (R01HG010881).

An experimental therapeutic cancer vaccine induced two distinct and desirable immune system responses that led to significant tumor regression in mice, report investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
The researchers found that intravenous (IV) administration of the vaccine boosted the number of cytotoxic T cells capable of infiltrating and attacking tumor cells and engaged the innate immune system by inducing type I interferon. The innate immune response modified the tumor microenvironment, counteracting suppressive forces that otherwise would tamp down T-cell action. Modification of the tumor microenvironment was not seen in mice that received the vaccine via needle injection into the skin (subcutaneous administration).
Dubbed “vax-innate” by the scientific team, the approach achieves an important goal in the quest for more effective immunotherapeutic vaccines for cancer. The study demonstrates that IV vaccine delivery enables and enhances T-cell immunity by overcoming tumor-induced immunosuppressive activity. The researchers say the candidate vaccine might also be given intravenously to people who have already received tumor-specific T cells as a therapy. It also could improve tumor control by increasing the number of T cells and altering the tumor microenvironment to make them function better, the researchers note.
The experimental vaccine, SNAPvax, was designed by Robert Seder, M.D., and colleagues at the NIAID Vaccine Research Center (VRC) together with collaborators from Vaccitech North America, a clinical-stage biopharmaceutical company in Baltimore, Maryland. Vaccitech announced plans to advance the SNAPvax platform for use in treating human papilloma virus-associated cancer in 2023.
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A typical gut bacterium that can spread through the body and cause a serious infection resists natural immune defenses and antibiotics by enhancing its protective outer layer, known as the cell envelope, according to a new study by Weill Cornell Medicine investigators. The finding suggests possible new ways to target these bacterial infections.
The research, published Nov. 10 in mBio, illuminates some of the underlying changes that may occur when Enterococcus faecalis (E. faecalis) populations move through the epithelial cells lining of the intestine and escape to reach other body sites.
“Systemic infections with E. faecalis can be lethal because this microbe has a remarkable ability to adapt to various environments and resist treatments,” said principal investigator Dr. Diana K. Morales, assistant professor of microbiology and immunology in obstetrics and gynecology at Weill Cornell Medicine. People at risk of developing these infections include those who are taking antibiotics or who have compromised immune systems, which facilitate E. faecalis overgrowth in the intestine. Understanding how E. faecalis moves out of the gut and spreads may one day help scientists find small molecules to stop the bacterium’s extra-intestinal dissemination, preventing dangerous infections.
How the bacterium can move out of the intestine and to other organs has remained largely unexplored. However, researchers have observed that two different populations of the same species of bacterium exist, Dr. Morales said. One population develops traits that allow it to pass through the intestinal barrier acquiring an advantageous resistance to antimicrobials, while the other stays put.
In a series of previous laboratory studies of the bacterium, the researchers found that motile E. faecalis produces molecules formed by sugar chains called polysaccharides that allow the bacterium to aggregate or clump together. “When these bacteria aggregate, they seem to develop an ability to move,” Dr. Morales said.
In the current study, the investigators, including lead author Dr. Yusibeska Ramos, a research associate in obstetrics and gynecology, found that the motile form of E. faecalis has a cell envelope containing increased amounts of glycolipids, which are fat molecules linked with a carbohydrate. Enhanced production of cell envelope glycolipids appears to help the bacterium to resist extracellular stressors. These stressors include the antimicrobial agent daptomycin, a common treatment for E. faecalis infection, and ?-defensins, small molecules intestinal epithelial cells produce to deter infection.
The researchers also found that genetic mutations that inhibit glycolipid production made E. faecalis more sensitive to these stressors and reduced the ability of the bacterium to penetrate cell surfaces and move through intestinal epithelial cells.
The next step for the researchers is to evaluate additional in vivo models to confirm whether the molecular pathways uncovered in the current study are needed for the bacterium to exit the intestine. “We are also interested in identifying pharmacological approaches that can target these specific pathways with the goal of one day helping patients better fight infections by this gut microbe,” Dr. Morales said.
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The nearly 200-year-old phrase “you are what you eat” has some new evidence. ISB researchers have found that the gut microbiome, including what we feed it, is largely responsible for the variation in circulating blood metabolites across people. This knowledge will help guide targeted interventions designed to alter the composition of the human blood metabolome. 
“We know that person-to-person variation in the blood metabolome — the small molecules found in the bloodstream that can interact with all the systems of our body — can tell us a lot about health and disease status. Figuring out what governs this variation is a necessary step that gets us closer to precision approaches to healthcare,” said Dr. Sean Gibbons, an ISB faculty member and co-corresponding author of the paper.
The research team examined 930 blood metabolites that were present in more than 1,500 individuals. Over 60 percent of the detected metabolites were significantly associated with either host genetics or the gut microbiome. “Notably, 69 percent of these associations were driven solely by the microbiome, with 15 percent driven solely by genetics and 16 percent were under hybrid genetic-microbiome control,” said ISB Senior Research Scientist Dr. Christian Diener, lead author of the study. Diener and co-lead author Chengzhen Dai analyzed the de-identified metabolomic, genomic, and microbiome data from consenting patients in a consumer scientific wellness program.
They found that the blood metabolite variation explained by the microbiome was largely independent of the variation explained by the genome, even for hybrid metabolites that were significantly associated with both genetics and microbes. Additionally, certain metabolite-microbe associations were only significant in individuals with specific genetic backgrounds, indicating a nuanced interplay between the microbiome and host genetics in shaping the blood metabolome.
These new findings are promising for a couple of reasons. First, the high number of microbiome-specific metabolites suggests that much of our blood metabolome could be modified through dietary, probiotic, and other lifestyle interventions. Second, metabolites that are under stricter genetic control may not be responsive to lifestyle modification, making them targets for pharmacological interventions that directly target host pathways.
“A deeper understanding of the determinants of the blood metabolome will provide us with a window into how these circulating metabolite levels can be engineered and optimized for health,” said Dr. Andrew Magis, co-corresponding author of the paper. “Understanding which circulating small molecules fall predominantly under host versus microbiome control will help guide interventions designed to prevent and/or treat a range of diseases.”
This research was supported by the National Institutes of Health under award number R01DK133468, as well as by funds from Dr. Gibbons’ Washington Research Foundation Distinguished Investigator Award. The content published in Nature Metabolism is solely the responsibility of the paper’s authors and does not necessarily represent the official views of the National Institutes of Health.
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An enzyme that drives the growth of an often-lethal childhood brain cancer may hold the key to a future treatment, says a McMaster University-led study.
Researchers discovered that by blocking the production of an enzyme called DHODH, they were able to halt the growth of MYC gene-amplified medulloblastoma in mouse models, the most aggressive subtype of this cancer.
First author William Gwynne said that while blocking DHODH stops the cancer spreading, healthy brain and nerve cells are spared. This will avoid the after-effects of current treatments, including radiotherapy and chemotherapy, which can impair children’s brain development even if their cancer is successfully treated.
“This potential treatment pathway will allow us to kill the weeds but save the flower of the developing brain,” said Gwynne, a post-doctoral researcher of the Centre for Discovery in Cancer Research
“This DHODH treatment target is full of promise, but it will take several years before we can reach the clinical trial stage. This potential new treatment, unlike current ones, will not be toxic to the developing brain.”
The study was published in the journal Cancer Cell on Nov. 10.

Scientists have used a proteomics approach to identify a three-protein signature in the blood that can improve detection of isolated impaired glucose tolerance, a form of prediabetes. The research, led by scientists from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, UK, and Berlin Institute of Health at Charité, Germany, is published today in Nature Medicine.
Medical and behavioural interventions in individuals with prediabetes are effective in delaying or preventing the onset of type 2 diabetes, but a substantial proportion of people with prediabetes are missed by current clinical screening and diagnostic techniques. Individuals with isolated impaired glucose tolerance (isolated IGT), a common subtype of prediabetes, can only be identified through oral glucose tolerance testing as they have normal results with more commonly undertaken tests. Oral glucose tolerance testing is a time-consuming procedure requiring repeated blood draws, and is not routinely performed as part of type 2 diabetes clinical screening strategies.
The authors used a proteomic assay to measure the levels of nearly 5,000 proteins in blood plasma samples from more than 11,000 participants in the Fenland Study, each of whom underwent an oral glucose tolerance test. The authors created a machine learning algorithm that was able to extract a core set of few proteins out of the thousands measured that were most informative in identifying people most likely to have isolated IGT in advance of undertaking an oral glucose tolerance test.
The authors identified a signature of only three proteins that when combined with standard screening techniques for impaired glucose tolerance improved identification of individuals with isolated IGT in the Fenland study cohort, and subsequently confirmed this finding in the independent Whitehall II study. Their results also indicate that fasting before the blood sample is taken does not significantly change the reliability of the three protein signature for identifying people with impaired glucose tolerance, which would greatly increase the application of the test in clinical practice.
PhD student Julia Carrasco Zanini, first author on the paper, said:
“The Fenland Study is unique for its size in combining genetic data and blood sampling with objective measurements of a range of clinical characteristics that includes oral glucose tolerance testing. By combining this resource with broad-capture proteomics technology we were able to identify protein signatures that substantially improved detection of impaired glucose tolerance.”
The authors suggest that by replacing the two-step screening strategy recommended by current guidelines with a three-step screening strategy that incorporates testing for the three-protein signature, the number of individuals who need to undergo oral glucose tolerance testing to identify an isolated IGT case could be substantially reduced. However, they note that some individuals with isolated IGT would still be missed, an important consideration for clinical implementation.
Senior author Professor Claudia Langenberg said:
“Our strategy has the potential to address an important unmet clinical need: the identification of a meaningful proportion of people with prediabetes who currently remain undetected. Early identification would enable preventive lifestyle and behavioural interventions to improve the health of affected individuals and alleviate the burden to health-care systems caused by their delayed diagnosis.
We would now like to evaluate the three-protein signature in other populations and ethnic groups, and ultimately to test the three step strategy for identifying prediabetes in randomised screening trials.”
The Fenland Study is funded by the Medical Research Council. Proteomic measurements were supported and governed by a collaboration agreement between the University of Cambridge and SomaLogic.
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