Category Archives: Immunology

Immunology

Researchers identify viable vaccine targets for hepatitis C infections – News-Medical.Net

By studying individuals who spontaneously clear hepatitis C infections, a team of researchers has identified viable vaccine targets for a disease that infects 70 million worldwide with case numbers increasing every year.

It turns out that a quarter of people who become infected with the hepatitis C virus clear the infection on their own without treatment, while the remaining three-quarters of people develop chronic infections that can last for years. The blood-borne disease which causes liver cirrhosis, liver failure and liver cancer is especially prevalent among people who inject drugs.

Direct-acting antivirals developed around a decade ago are 98% effective. But even so, the number of hepatitis C cases has increased year-over-year mainly because early infections are hard to detect, access to treatment is limited and reinfections occur even after treatment.

"That's why there is now a big interest in developing a hepatitis C vaccine," saidAndrew Flyak, assistant professor of microbiology and immunology in the College of Veterinary Medicine and co-corresponding author of the study, "Convergent Evolution and Targeting of Diverse E2 Epitopes by Human Broadly Neutralizing Antibodies are Associated with HCV Clearance," which published March 21 in the journal Immunity. Justin Bailey, associate professor of medicine at Johns Hopkins University, is co-corresponding author.

Our study gives us a glimpse into how certain individuals clear a highly variable infection, and we believe this information can inform a vaccine development."

AndrewFlyak, assistant professor of microbiology and immunology in the College of Veterinary Medicine and co-corresponding author of the study

The study was made possible due to the unique access that Bailey had to samples from people who injected drugs and were at risk of acquiring the virus. This allowed the researchers to track individuals who were hepatitis C negative when they enrolled in the program, and to see upon subsequent clinic visits whether that person acquired the virus. Bailey obtained samples from individuals who cleared the infection on their own and those who developed chronic infection.

Viruses that evolve very rapidly, such as SARS-CoV-2, influenza and hepatitis C, have extraordinary genetic diversity with multiple strains. Combating these types of infections requires special antibodies (blood proteins that recognize pathogens and neutralize them) called broadly neutralizing antibodies (bNAbs), which can neutralize diverse viral variants.

In previous studies, researchers isolated bNAbs from people who were chronically infected with hepatitis C virus. They found that their bNAbs were using a single antibody gene to encode a variable part of the antibody molecule.

"In order to make an antibody, immune systems use multiple sets of different antibody genes, but for whatever reason the immune systems in people with chronic hepatitis C infections used just one variable antibody gene, called VH1-69," Flyak said. Also, most of the bNAbs from these chronically infected donors targeted a specific region of the hepatitis C virus, namely the front layer of the so-called E2 protein. The immune system in chronically infected individuals has failed to clear the virus.

In the current study, the researchers isolated bNAbs from one person who spontaneously cleared three separate infections. This individual's bNAbs revealed important distinctions. First, these bNAbs were genetically diverse, meaning they are encoded by a variety of variable genes, and not just one segment of the VH1-69 gene. Second, bNAbs from this individual targeted three different regions of the virus' E2 protein, the front layer, as well as a back layer and a b-sandwich.

The data suggests that a hepatitis C virus vaccine should elicit bNAbs to all three regions of the E2 protein rather than just one region of the virus, Flyak said.

"If you have a response to multiple regions, you can have a synergistic effect, you get a response that is much stronger than the sum of its parts," he said.

BNAbs from the individual who cleared the infections also revealed evidence of what is called convergent evolution, where different bNAbs have the same mutations but come from different antibody variable genes. "You see the same mutations in two different broadly neutralizing antibodies it means those mutations are important," Flyak said and they increase the breadth of the antibody response to hepatitis C virus.

Members of Flyak's lab used X-ray crystallography to solve the crystal structures of bNAbs in complex with hepatitis C virus' E2 protein and show how bNAb's mutations interact with the E2 protein. "That information can be used to design better vaccine candidates," Flyak said.

In next steps, the team will collaborate with a larger international group to screen multiple vaccine candidates in animals and eventually identify which ones to bring into human clinical trials.

Clinton Ogega, a former graduate student in Bailey's lab, is the paper's first author. Two postdoctoral fellows in Flyak's lab, Marty Schoenle and Xander Wilcox, contributed to the study.

The study was supported by the National Institutes of Health.

Source:

Journal reference:

Ogega, C. O., et al. (2024). Convergent evolution and targeting of diverse E2 epitopes by human broadly neutralizing antibodies are associated with HCV clearance.Immunity. doi.org/10.1016/j.immuni.2024.03.001.

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Researchers identify viable vaccine targets for hepatitis C infections - News-Medical.Net

Immunology

Multiple sclerosis has distinct subtypes, study finds, pointing to different treatments – STAT

For years, researchers have been hopeful they could get under the hood of multiple sclerosis. The neurological condition shows up in over 2.5 million people around the world, but it doesnt always look the same. If science could point its light in just the right way, patients might be sorted into disease subgroups, and treated more successfully depending on their kind of MS.

A new study out of Germany gives it a shot, offering up three MS subtypes based on immune markers found in patients blood each group with slightly different disease progression.

The MS connection of the senior author, Heinz Wiendl, could start in his home. His mother had the condition. But thats not really it, he says. He was always fascinated by immunology and neurology, and how MS went from an untreatable disease to a known, druggable condition in less than 40 years.

Hes been in the field for more than half of that time, trying to get a grasp on how the immune system fusses and frays in response to antigens, and how that turns into a difficult chronic condition. MS causes vision problems, fatigue, and weakness or spasms in the arms and legs, among a host of other symptoms. The condition is thought to be more common in women.

Most recently, Wiendl set out to prove a hypothesis hes been building for years: that MS patients have immunological signatures in their blood that match certain versions of the same disease.

With collaborators at a half dozen institutions across Germany, Wiendl, a professor of neurology at the University of Mnster, launched a multi-center cohort study of 500 patients with early-stage MS. Those newly sick people were a right fit because the immunological derailment has happened, but its not yet spread out and diverged, he said. Plus, patients hadnt undergone treatments that changed their immune systems.

And Wiendl, with all his years of research, tried to wipe his mind clean of all presuppositions he had about the disease and go in agnostic. The team assessed the quantity and quality of various immune cell populations, not favoring any in particular. And then they let an algorithm determine whether certain cell populations, or a combination of them, were more prevalent in these MS patients.

Its a little like Lebron James, Wiendl said. If the cameraman is only ever focused on James, the audience will miss what the other players are doing. Sure, the superstar or highly suspect immune cell is captivating, but viewers could miss important plays elsewhere on the court.

If Lebron James in the end happens to make the most goals or baskets, we will find out anyway. But we have not overlooked the others, he said. This is the unsupervised approach the team used.

In the end, there was some superstar-watching: The researchers confirmed that players other researchers had spotted in MS were playing a role in their cohorts, too. But they also found new things, published Wednesday in Science Translational Medicine.

Most notably, Wiendl and his collaborators say they found unique stamps of immunological activation that correspond to specific subgroups, or endophenotypes. And each subgroup identified as E1, E2, and E3 had its own disease trajectory when they followed patients for four years.

E1 patients had alterations in the CD4 T cell compartment, the helper cells that can activate other immune cells, and inflammatory proteins that have been associated with autoimmune disease. This group was associated with earlier structural brain damage, greater disease severity, and higher disability their condition was much worse from the beginning, Wiendl said.

Meanwhile, E2 had differences in natural killer cells, which take down sick cells. And E3 patients had changes to highly toxic CD8 T cells, making it a more inflammatory category. E3 patients had a higher relapse rate within the first year, and more MS lesions that point to issues in the blood-brain barrier. Researchers also found more immune cells in the cerebrospinal fluid of E3 patients (this data was available for about 170 of the patients).

There was some overlap, but Wiendl and his colleagues believe the subtypes are distinct and could help predict how patients disease progresses. They dont know exactly how stable the subtypes are over longer periods of time, or if treatment changes it. But Wiendl said cellular signatures were found over time in the handful of patients who went untreated, including up to nine years within one individual, the authors note in the study.

These differing subgroups could suggest the disease arises through a multitude of immune system pathways. Not only that, Wiendl said, but the groups responded differently to treatments over time potentially a valuable insight for drug developers and clinicians.

For example, the inflammatory E3 group for the most part didnt respond to treatment with interferons, commonly used disease-modifying therapies first approved for MS in 1993. But these patients did improve by taking monoclonal antibodies, such as alemtuzumab (Sanofi Genzymes Lemtrada) and ocrelizumab (Genentechs Ocrevus).

The ability of the endophenotypes to predict a patients future condition needs to be checked by other researchers, and in a different population, said Alberto Ascherio, who led a pivotal study linking MS to previous Epstein-Barr infection and was not involved in the German study. He called the new study interesting for those in the field and said that endophenotypes could, in theory, help to personalize treatment.

But the science isnt there yet, Ascherio added. Personalized medicine in MS is still a fashionable word that is more a marketing pitch than a reality.

Wiendl said he hopes other researchers can use the studys data to test and confirm how well different MS treatments work for patients with these immune signatures, and to find other potential therapies. Wiendl also programmed an app with the data, and said he is developing a test to help others discriminate between the E subgroups. His spinoff company has patented the endophenotypes.

Ideally, one day there will be a simple test to classify patients and help doctors find the most effective treatment, Wiendl said.

We really want to transform patient care and not just open the door, he said.

STATs coverage of chronic health issues is supported by a grant fromBloomberg Philanthropies. Our financial supportersare not involved in any decisions about our journalism.

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Multiple sclerosis has distinct subtypes, study finds, pointing to different treatments - STAT

Immunology

Three research projects awarded funding from the Immunology Institute Pilot Project program – University of Alabama at Birmingham

The program seeks to support and foster multidisciplinary collaborations, especially between UAB clinicians and basic and physician scientists.

The program seeks to support and foster multidisciplinary collaborations, especially between UAB clinicians and basic and physician scientists.The University of Alabama at Birminghams Immunology Institute Pilot Project program has selected three research projects to award funding during its inaugural year.

The three projects awarded include:

The pilot grant program received matching funding from the ONeal Comprehensive Cancer Center at UAB, so the three awarded projects will be funded for one to two years.

The pilot grant program is housed in the Marnix E. Heersink School of Medicines Immunology Institute and serves as a central focal point for coordinating immunologic research across various disciplines. The program seeks to support and foster multidisciplinary collaborations, especially between UAB clinicians and basic and physician scientists.

UAB immunology-focused investigators actively explore the power of the immune system to treat and prevent infectious diseases, transplant organ rejection, autoimmunity, allergy, cancer and numerous inflammatory-based conditions.

Applications for 2025 funding opportunities will open later this fall.

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Three research projects awarded funding from the Immunology Institute Pilot Project program - University of Alabama at Birmingham

Immunology

Deal Watch: AbbVie Adds To Immunology Pipeline Through Deal With OSE – Scrip

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Immunology

AbbVie and Tentarix Announce Collaboration to Develop Conditionally-Active, Multi-Specific Biologics for Oncology … – PR Newswire

NORTH CHICAGO, Ill. and SAN DIEGO, Feb. 22, 2024 /PRNewswire/ -- AbbVie Inc. (NYSE: ABBV) and Tentarix Biotherapeutics today announced a multi-year collaboration focused on the discovery and development of conditionally-active, multi-specific biologic candidates in oncology and immunology. The collaboration will integrate AbbVie's expertise in oncology and immunology with Tentarix's proprietary Tentacles platform.

Tentacles are multi-functional, conditionally-active antibody-based biologics that are designed specifically to activate immune cells that can modulate disease pathways, while potentially mitigating safety concerns associated with non-specific targeting of other immune cells.

"Oncology and immunology are two of our key strategic growth areas where we are pursuing novel technologies that aim to deliver transformative therapies, which address unmet patient needs," said Jonathon Sedgwick, Ph.D., senior vice president and global head of discovery research, AbbVie. "This strategic partnership complements our ongoing efforts in developing novel biologics, potentially to expand our oncology and immunology portfolios with conditionally-active multi-specific molecules."

"We are excited to join forces with AbbVie to help accelerate cutting-edge, conditionally-active therapeutic programs towards clinical applications for patients in need," said Don Santel, interim chief executive officer, Tentarix Biotherapeutics. "This collaboration adds to our portfolio of internal and external pipeline programs and is a strong validation of our approach in understanding and targeting complex immune interactions that drive cancers and inflammatory diseases."

Under the terms of the agreements, Tentarix will receive upfront option payments, totaling $64 million from AbbVie, for the two programs. AbbVie will receive an exclusive option to fully acquire the programs following candidate nomination, for an additional undisclosed payment for each program.

About AbbVieAbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas immunology, oncology, neuroscience, and eye care and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us atwww.abbvie.com. Follow @abbvie onLinkedIn,Facebook,Instagram,X (formerly Twitter), andYouTube.

About TentarixTentarix's mission is to develop first-in-class targeted, multifunctional, conditional therapies across a range of indications of high unmet medical need. Tentarix is focused on modulating cell specific functions while increasing the safety profile for biologics. Tentarix has built a team that aims to transform research and development through understanding complex immune interactions (CellSurf), discovery of novel human antibodies (HuTARG), and high-throughput screening of conditional multi-specifics (FunctionSeq). For more information, please visit http://www.tentarix.com.

AbbVie Forward-Looking StatementsSome statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 AnnualReport on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

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AbbVie and Tentarix Announce Collaboration to Develop Conditionally-Active, Multi-Specific Biologics for Oncology ... - PR Newswire

Immunology

Integrating single-cell multi-omics and prior biological knowledge for a functional characterization of the immune system – Nature.com

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Immunology

Renowned immunologist and four-decade UAB researcher Max Cooper, M.D., will deliver this year’s Marx Lecture – University of Alabama at Birmingham

Cooper recently won the Albert Lasker Award, known as Americas Nobel Prize, given to the living person considered to have made the greatest contribution to medical science.

Max Cooper, M.D., Photo Credit: Emory UniversityMax Cooper, M.D., a distinguished immunologist and 40-year career veteran of the University of Alabama at Birmingham, will return to UAB on March 11 to present this years 36th Bertram M. Marx Endowed Lecture, hosted by the UAB Department of Microbiology.

Cooper is known for his research characterizing T cells and B cells and his numerous unprecedented contributions to the field of immunology.

Dr. Cooper is a towering figure in the field of immunology, said J. Victor Garcia-Martinez, Ph.D., chair of the UAB Department of Microbiology. He literally wrote the book on B cell biology and the adaptive immune system. His discoveries have transcended generations of scientists, and his impact has shaped modern immunology in numerous ways. He is an outstanding role model for young scientists.

Cooper, a professor in the Department of Pathology and Laboratory Medicine and the Emory Vaccine Center at the Emory University School of Medicine, came to UAB in 1967 as a professor in the Division of Pediatric Allergy and Immunology of the Department of Pediatrics and as an associate professor in the Department of Microbiology.

He went on to become a professor in the Department of Microbiology and was also involved with UABs ONeal Comprehensive Cancer Center, the Comprehensive Arthritis, Musculoskeletal, Bone and Autoimmunity Center, and the Cystic Fibrosis Research Center.

Cooper moved to Emory University in 2008 but remains a professor emeritus of Medicine at UAB. He is also an Emory University School of Medicine Eminent Scholar, Georgia Research Alliance investigator and investigator at the Emory Center for AIDS Research.

Among his many notable awards, Cooper became UABs first member of the National Academy of Sciences in 1988 and was named to the National Academy of Medicine in 1990. He received the American Association of Immunologists Lifetime Achievement Award in 2000, was inducted as a foreign member of the British Royal Society in 2017 and received the Japan Prize in 2018.

In 2019, Cooper, together with Jacques Miller, was awarded the Albert Lasker Award for Basic Medical Research, an award that frequently precedes a Nobel Prize in Medicine. The Lasker Award, known as Americas Nobel Prize, is given by the Lasker Foundation to the living person considered to have made the greatest contribution to medical science.

Dr. Max Coopers contributions to the field of immunology and medicine at large characterize him among the most distinguished scientists to have called UAB home, said Anupam Agarwal, M.D., senior vice president for Medicine and dean of the Marnix E. Heersink School of Medicine. I am thrilled that he is returning to share his invaluable insights with the UAB research community.

The 36th Bertram M. Marx Lectureship will take place Monday, March 11, at 3 p.m. in-person in Room 102, the Cudworth Building. Cooper will present Evolution of Lymphocyte-Based Immunity. A reception will follow in the Bevill Biomedical Research Building lobby.

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Renowned immunologist and four-decade UAB researcher Max Cooper, M.D., will deliver this year's Marx Lecture - University of Alabama at Birmingham

Immunology

Inactivation of TGF- signaling in CAR-T cells | Cellular & Molecular Immunology – Nature.com

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Immunology

Babies use their immune system differently but efficiently | Cornell Chronicle – Cornell Chronicle

Scientists have long believed that a newborns immune system was an immature version of an adults, but new research shows that newborns T cells white blood cells that protect from disease outperform those of adults at fighting off numerous infections.

These results help clarify why adults and infants respond differently to infectionsand pave the way for controlling T cells behavior for therapeutic applications.

This discovery was described in a paper, The Gene Regulatory Basis of Bystander Activation in CD8+ T cells, which published Feb. 23 in the journal Science Immunology. Brian Rudd, associate professor in the Department of Microbiology and Immunology in the College of Veterinary Medicine, and Andrew Grimson, professor in the Department of Molecular Biology and Genetics (College of Arts and Sciences), co-led the study.

The immune system is almost always viewed from an adult perspective, Rudd said. For example, adult T cells outperform newborn T cells at tasks including recognizing antigens, forming immunological memory and responding to repeat infections, which has led to the belief that infants T cells were just a weaker version of the adult ones. But during the COVID-19 pandemic, many were surprised by the apparent lack of illness in infants, bringing this long-standing belief into question.

Interested in understanding these age-related differences, Rudd and Grimson discovered that newborn T cells are not deficient. Instead, they are involved in a part of the immune system that does not require antigen recognition, the innate arm of the immune system. While adults T cells use adaptive immunity recognizing specific germs to then fight them later newborn T cells are activated by proteins associated with innate immunity, the part of the immune system that offers rapid but nonspecific protection against microbes the body has never encountered.

Our paper demonstrates that neonatal T cells are not impaired, they are just different than adult T cells and these differences likely reflect the type of functions that are most useful to the host at distinct stages of life, Rudd said.

Neonatal T cells can participate in the innate arm of the immune system. This enables newborns T cells to do something that most adult T cells cannot respond during the very first stages of an infection and defend against a wide variety of unknown bacteria, parasites and viruses.

We know that neonatal T cells dont protect as well as adult T cells against repeat infections with the same pathogen. But neonatal T cells actually have an enhanced ability to protect the host against early stages of an initial infection, Rudd said. So, it is not possible to say adult T cells are better than neonatal T cells or neonatal T cells are better than adult T cells. They just have different functions.

The team also found that these innate neonatal T cells persist into adulthood in both mice and humans and play unique roles during infection. The team believes that in adults, these neonatal T cells may respond to inflammation that occurs during an infection, in cancer and in autoimmune diseases.

As part of their research, Rudd and his collaborators identified the molecular mechanisms that allow T cells to respond to inflammation and switch between innate and adaptive functions.

We now know the key epigenetic and transcriptional programs that distinguish neonatal T cells from adult T cells at the individual cell level, Rudd said. This knowledge is essential to developing medical applications for controlling T cells behavior in specific ways.

The technology that is now available to study gene regulation of immune cells at the single-cell level allowed Rudd and Grimson to provide new insight into a poorly understood biological process at a very in-depth level.

Being able to go from observing a unique function of T cells to a molecular mechanism is really exciting, Rudd said. And this was possible because we were able to combine the expertise in cellular and developmental immunology in my lab with the tools to study gene regulation in Andrews lab.

Following up on his discovery, Rudd wants to study the neonatal T cells that persist into adulthood in humans. We are also interested in studying how changes in the relative numbers of neonatal T cells in adults contributes to variation in the susceptibility to infection and outcomes to disease, he said.

The large, multi-institution project also included collaborators at University of Rochester and University of Washington.

This work was supported by the National Institute of Allergy and Infectious Disease and the National Institute of Child Health and Human Development, in the National Institutes of Health.

Elodie Smith is a writer for the College of Veterinary Medicine.

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Babies use their immune system differently but efficiently | Cornell Chronicle - Cornell Chronicle

Immunology

Antibody reduces allergic reactions to multiple foods in NIH clinical trial – National Institutes of Health (NIH) (.gov)

News Release

Sunday, February 25, 2024

Drug can help protect kids with multiple food allergies during accidental exposure.

A 16-week course of a monoclonal antibody, omalizumab, increased the amount of peanut, tree nuts, egg, milk and wheat that multi-food allergic children as young as 1 year could consume without an allergic reaction in a late-stage clinical trial. Nearly 67% of participants who completed the antibody treatment could consume a single dose of 600 milligrams (mg) or more of peanut protein, equivalent to 2.5 peanuts, without a moderate or severe allergic reaction, in contrast with less than 7% of participants who received placebo. The treatment yielded similar outcomes for egg, milk, wheat, cashew, walnut and hazelnut at a threshold dose of 1,000 mg protein or more. This suggests the antibody therapy has the potential to protect children and adolescents if they accidentally eat a food to which they are allergic despite efforts to avoid it, according to the investigators. The findings were presented today at the American Academy of Allergy, Asthma & Immunology Annual Meeting in Washington, D.C., and published in The New England Journal of Medicine.

People with food allergies and their caregivers need to maintain constant vigilance to avoid foods that could cause a potentially life-threatening allergic reaction. This is extremely stressful, especially for parents of young children, said Jeanne Marrazzo, M.D., M.P.H., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health and the trials regulatory sponsor. Although food avoidance remains critical, the findings reported today show that a medicine can help reduce the risk of allergic reactions to common foods and may provide protection from accidental exposure emergencies.

NIAID funds the ongoing trial with additional support from and collaboration with Genentech, a member of the Roche Group, and Novartis Pharmaceuticals Corporation. The two companies collaborate to develop and promote omalizumab, marketed as Xolair, and are supplying it for the trial. The National Center for Advancing Translational Sciences, also part of NIH, supports some of the staff, space and services used to conduct the trial.

An estimated 7.6% of children in the United State roughly 5.5 million kids have food allergies. On February 16, 2024, the Food and Drug Administration approved omalizumab for the reduction of allergic reactions, including anaphylaxis, that may occur with an accidental exposure to one or more foods in adults and children aged 1 year and older with food allergy. The FDA approval was based on data from a planned interim analysis of the Phase 3 NIAID trial. People taking omalizumab still need to avoid foods they are allergic to. Omalizumab is not approved for the emergency treatment of allergic reactions, including anaphylaxis.

Previously, the only available treatment for food allergy was oral immunotherapy, or OIT, which involves daily ingestion of a specific food allergen in gradually increasing doses up to a maintenance amount.

The multi-stage trial is called Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Children and Adults, or OUtMATCH. The first stage of the study was designed to see if taking omalizumab increased the threshold for the amount of food that caused allergic reactions, thereby reducing the likelihood of reactions to small amounts of food allergens during accidental exposure.

Omalizumab works by binding to the allergy-causing antibody called immunoglobulin E in the blood and preventing it from arming key immune cells responsible for allergic reactions. This renders these cells much less sensitive to stimulation by any allergen.

The NIAID-funded Consortium for Food Allergy Research (CoFAR) is conducting OUtMATCH at 10 locations across the United States. The CoFAR has enrolled 177 children and adolescents ages 1 to 17 years and three adults ages 18 to 55 years, all with confirmed allergy to peanut and at least two other common foods among milk, egg, cashew, wheat, hazelnut or walnut.

In the first stage of the trial, people who reacted to small amounts of food allergens during oral food challenges were assigned at random to receive injections of either omalizumab or placebo. Neither the participants nor the investigators knew which food was used in a challenge nor who was in which group. After 16 to 20 weeks of injections, the participants were challenged again in a carefully controlled setting to see if they could tolerate a greater amount of food than they did at the outset. The goal was to find out if omalizumab injections led to a statistically significant increase in the proportion of participants who could consume roughly the equivalent of 2.5 peanuts without a moderate or severe allergic reaction, up from less than half a peanut at the outset, and similarly greater quantities of milk, egg or cashew among people allergic to those foods.

Investigators found that omalizumab was superior to placebo in increasing the reaction threshold for peanut, milk, egg and cashew as well as wheat, walnut and hazelnut to levels that likely would protect against allergic reactions upon accidental exposure. Seventy-nine of 118 omalizumab-treated children and adolescents, or 66.9%, could consume at least a single dose of 600 mg or more of peanut protein without a moderate or severe allergic reaction during the post-treatment challenge, in contrast with four out of 59 children and adolescents, or 6.8%, who received placebo. The researchers observed similar results for milk, egg, cashew, wheat, walnut and hazelnut at a threshold dose of 1,000 mg protein or more.

Many omalizumab-treated participants ate more than 600 mg of peanut protein without a moderate or severe allergic reaction. Sixty-seven percent consumed a cumulative dose of 1,044 mg of peanut protein, or about four peanuts, and 44% ate a cumulative dose of 6,044 mg of peanut protein, or about 25 peanuts. In addition, substantial proportions of treated participants consumed a cumulative dose of 1,044 mg of more than one food without a moderate or severe allergic reaction. Sixty-nine percent ate this amount of two foods, and 47%, three foods.

The first 60 participants who completed the first stage entered a 24-week open-label extension of omalizumab injections followed by additional oral food challenges. Most participants who had received omalizumab in the first stage maintained or increased the amount of food protein they could consume without an allergic reaction during the extension.

Robert Wood, M.D., and Sharon Chinthrajah, M.D. are leading the trial. Dr. Wood is the Julie and Neil Reinhard Professor of Pediatric Allergy and Immunology and director of the Pediatric Clinical Research Unit at the Johns Hopkins University School of Medicine. Dr. Chinthrajah is an associate professor of medicine and of pediatric allergy and clinical immunology at Stanford University School of Medicine.

Further information about the ongoing OUtMATCH trial is available at ClinicalTrials.gov under study identifier NCT03881696. The outcomes of later stages of the trial will be published in the future.

NIAID conducts and supports researchat NIH, throughout the United States, and worldwideto study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

RA Wood, et al. Omalizumab for the treatment of multiple food allergy. The New England Journal of Medicine DOI: 10.1056/NEJMoa2312382. (2024).

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