(Press-News.org) COLUMBUS, Ohio – Scientists have engineered a monoclonal antibody that can protect mice from a lethal dose of influenza A, a new study shows. The new molecule combines the specificity of a mature flu fighter with the broad binding capacity of a more general immune system defender.
The protective effect was enhanced by delivering the antibody in a nasal spray that disperses these molecules throughout the respiratory tract, where they stick to the slippery mucus lining to lie in wait for invading viral particles.
The engineered molecule is based on the IgM version of an immunoglobulin antibody, the generic first line of antibody defense against infection – but with an added structural feature that attaches to a very specific location on the influenza A surface to neutralize the virus.
“It’s a better platform with a better antibody. If we can prepare the respiratory environment with this enhanced engineered molecule, it can capture and intercept the virus in an early stage,” said co-lead author Kai Xu, assistant professor of veterinary biosciences at The Ohio State University. “This would be a therapy that not only can be used for prevention of seasonal flu – it potentially could also be used against pandemic strains in the future.”
The study was published April 29 in Nature Communications.
Influenza A viruses are divided into subtypes based on characteristics of two major surface proteins, hemagglutinin (HA) and neuraminidase (NA) – as in, for example, the strain annually circulating in people, H1N1, and a less common H3N2 virus that co-circulates during flu season.
Previous work has shown that monoclonal IgG antibodies engineered to target the influenza A HA protein lose potency as the virus mutates its way out of their crosshairs.
These antibodies, mimicking mature natural flu-fighters of the adaptive immune system, attach to a precise section of the surface protein to disable the virus’s ability to bind to a host cell receptor and enter the cell to make copies of itself. But once viruses figure out where they’re being targeted by antibodies, they mutate those sites to escape recognition by the immune system.
Xu and colleagues theorized that building an anti-flu antibody based on the IgM isotype – an early, first-line immune responder known for its pentameric shape – featuring more structural sites capable of binding to the HA protein as well as an IgG-level tight and precise target, would increase the antibody’s neutralization capacity.
The team constructed and evaluated 18 IgM antibodies based on existing IgG antibodies known to target different segments of the HA protein, landing on one IgM version that was superior in cell culture studies at neutralizing a panel of H1N1 and H3N2 flu viruses that have been circulating in people for at least 50 years.
“The advantage is that we utilized the multivalency feature of IgM combined with the potency of a mature broadly neutralizing antibody,” Xu said. “Multivalent means that this molecule has multiple arms to capture the virus, so the virus has very little chance to escape.
“And because IgM is a large molecule, when it binds to the viral surface it effectively covers the surface, so it prevents receptor engagement.”
Experiments showed that even if a mutation affected this IgM antibody’s strong attraction to a specific HA binding site, the antibody’s large size and multivalency could help it outpace viral escape attempts.
“By enhancing the capacity for it to recognize the mutated or differentiated viral surface regions, it can cross-protect against different influenza virus infections and can also work even after mutations occur,” Xu said.
In mouse experiments, researchers delivered a single dose of the IgM antibody in a nasal spray, intending to place a layer of the engineered antibody across the mucosal surfaces of the nasal cavities and lungs.
“The primary purpose is to refuse viruses before they can get into a host cell,” Xu said. “The mucosal immunity is more efficient than systemic immunity at intercepting, so the initial infection can be reduced or eliminated.”
Researchers followed the preventive nasal spray with lethal doses of H1N1 and H3N2 flu viruses. Compared to control animals that did not receive preventive treatment, mice receiving the IgM antibody had better outcomes: No mice got sick from the H3N2 strain, and most survived the H1N1 infection and recovered from symptoms.
The molecules remained on the mouse mucosal surface for seven days, an indication that a single spray could last for weeks in humans.
“The adhesiveness of the molecule extends its protection window, and that’s one advantage of this strategy,” Xu said.
Though this work focused on historic and seasonal versions of influenza A, Xu said the team of structural biologists, immunologists and virologists see the findings as a proof of principle to help establish the IgM platform as a potential therapeutic technology for different viruses – including bird flu, an influenza A H5 virus – and even non-viral diseases like cancer.
Xu co-led the study with Xinli Liu of the University of Houston, Tong-Ming Fu of IGM Biosciences Inc. and Zhiqiang An of the University of Texas Health Science Center at Houston. Additional co-authors from those institutions and the National Institute of Allergy and Infectious Diseases also worked on the study.
This research was supported by grants from the National Institutes of Health, IGM Biosciences and the Welch Foundation.
#
Contact: Kai Xu, Xu.4692@osu.edu
Written by Emily Caldwell, Caldwell.151@osu.edu; 614-292-8152
END
What makes people think an AI system is creative? New research shows that it depends on how much they see of the creative act. The findings have implications for how we research and design creative AI systems, and they also raise fundamental questions about how we perceive creativity in other people.
‘AI is playing an increasingly large role in creative practice. Whether that means we should call it creative or not is a different question,’ says Niki Pennanen, the study’s lead author. Pennanen is researching AI systems at Aalto University and has a background in psychology. ...
(Santa Barbara, Calif.) — Nicknamed the “king of the kelp forest,” giant sea bass are among scuba divers’ favorite characters to spot off the California Coast. But very few of these charismatic fish remain.
A team led by researchers at UC Santa Barbara has conducted the first direct population estimate of this critically endangered species in Southern California. Using photos sourced from the diving community, they found slightly more than 1,200 adult giant sea bass within Southern California waters from 2015 to 2022. The results, published in the Marine Ecology Progress Series represent an increasing trend in their numbers, suggesting ...
Drowning is the leading cause of unintentional death for children aged 1 to 4 in Florida, and children with autism face even greater danger – many times more likely to drown than their neurotypical peers. One key factor behind this alarming statistic is wandering, also known as elopement. Nearly 50% of children with autism will wander from a safe environment at some point. These incidents can happen in a split second and often lead to children being drawn to nearby water sources such as pools, ponds or canals – many of which are unprotected.
Children ...
In a research paper, scientists from the Tsinghua University proposed a novel enhanced Digital Light Processing (DLP) 3D printing technology, capable of printing composite magnetic structures with different material sin a single step. Furthermore, a soft robot with a hard magnetic material-superparamagnetic material composite was designed and printed.
The new research paper, published Feb. 26 in the journal Cyborg and Bionic Systems, introduces a soft robot based on DLP 3D printing technology, which presents extensive potential for the design and manufacturing of multifunctional soft robots.
According to Wang, "various ...
Researchers at Umeå University, Sweden, and Michigan State University, USA, have discovered a type of molecule that can kill chlamydia bacteria but spare bacteria that are important for health. The discovery opens the door for further research towards developing new antibiotics against chlamydia, the world's most common bacterial sexually transmitted disease with 130 million cases a year.
"No one should have to live with chlamydia. But the problem is that the treatments we have today do not distinguish between dangerous and friendly bacteria. A growing problem is ...
In recent years, the world has seen a surge in new and deadly infectious diseases, posing a major threat to global health. Outbreaks of COVID-19, H1N1 (swine flu), Ebola, Zika, and monkeypox are a stark reminder of our vulnerability. While some of these viruses are new and relatively unknown, others, like the monkeypox virus (mpox virus or MPXV) have been around since the 1970s but have been endemic to parts of Africa. However, the recent global outbreak of mpox—caused by a newly identified variant that is more infectious than previous strains—has raised concerns across the world, ...
UVA Health scientists are calling for clinical trials testing the potential of HIV drugs called NRTIs to prevent Alzheimer’s disease after discovering that patients taking the drugs are substantially less likely to develop the memory-robbing condition.
The researchers, led by UVA’s Jayakrishna Ambati, MD, previously identified a possible mechanism by which the drugs could prevent Alzheimer’s. That promising finding prompted them to analyze two of the nation’s largest health insurance databases ...
The incidence of infection by Mycobacterium abscessus, is increasing in patients with cystic fibrosis, chronic obstructive pulmonary disease (COPD), and other chronic pulmonary diseases, leading to an accelerated lung function decline. Remarkably, 58–78% of patients with M. abscessus infection are also infected with Pseudomonas aeruginosa, the most common pathogen in these conditions. However, how these two bacterial species interact during infection remains poorly understood.
Now, a new study led by the Institute for Bioengineering of Catalonia (IBEC) and the Universitat ...
Consumption of ultra-processed foods, such as sugar-sweetened beverages, potato chips and packaged cookies, may be associated with adverse health outcomes, according to research being presented at the ACC Asia 2025 Together with SCS 36th Annual Scientific Meeting taking place May 9-11 in Singapore. This risk for hypertension, other cardiovascular events, cancer, digestive diseases, mortality and more, increased with every 100 grams of ultra-processed foods consumed each day.
“Ultra-processed foods are characterized by high sugar, high salt, and other non-nutritive components, exhibiting low nutritional density yet ...
Twenty-eight major U.S. cities, including New York, Dallas, and Seattle, are seeing urban areas sink by 2 to 10 millimeters per year, according to new research from Virginia Tech. The major cause is groundwater extraction.
Published in Nature Cities, the study used satellite-based radar measurements to create high-resolution maps of subsidence, or sinking land, for 28 of the most populous U.S. cities. The cities are home to 34 million people, about 12 percent of the total U.S. population.
In every city studied, at least 20 percent of the urban area ...
