Category Archives: Immunology

Immunology

Measles outbreaks show the risk of under-vaccination | News | Harvard T.H. Chan School of Public Health – HSPH News

March 27, 2024On March 18, the Centers for Disease Control and Prevention issued a health alert warning clinicians and public health officials of a global rise in measles cases. Yonatan Grad, professor of immunology and infectious diseases at Harvard T.H. Chan School of Public Health, discusses the highly transmissible disease and what may be driving its resurgence.

Q: What should the public know about measles?

A: The first thing that people should know is that measles is preventable. The measles vaccine is one of our best. One dose is 93% effective and two doses are 97% effective in protecting against infection.

Second, measles is extremely contagiousone of the most contagious pathogens we know of. In a classroom of children who are not protected against measles, a child with measles will infect 12-18 others.

Third, measles can lead to severe health consequences. About 1 in 5 unvaccinated people with measles are hospitalized. About 1 in 20 get pneumonia. About 1 in 1000 get encephalitisinflammation of the brainwhich can result in intellectual disabilities. And about 1 to 3 in 1000 die, most often from measles pneumonia.

Another thing thats not well appreciated is that measles can cause immune amnesia, in that it resets immunity to other diseases. When the vaccine was rolled out, there was not only a decline in measles, but also declines in other childhood infections like chickenpox. Recent work showed how measles infection depletes your antibodies, making you more susceptible to pathogens you had developed protection against. So the benefit of measles vaccination is two-fold: It protects people from measles and helps maintain protection against other childhood illnesses.

Q: Across the U.S. and around the world, were seeing measles cases rise. What might be driving this resurgence?

A: The key issue here is under-vaccination. To protect a community from outbreaks, about 95% of the population needs to have been vaccinated. In some low-income countries, the rates are down around 60-70%, and weve seen large measles outbreaks and measles-related deaths in those areas. Childhood vaccination and preventive health care was disrupted with the COVID-19 pandemic, putting these populations at even greater risk.

In the U.S., where the high rate of vaccination was a tremendous success in reducing measles, anti-vax trends have led to communities becoming more susceptible. Most of the recent U.S. cases have been related to international travel, and then those cases have sparked outbreakslike the ones in the past few months in Philadelphia and Broward County, Florida.

Q: The drop in vaccination rates is alarming. What are some of the cultural and political drivers that are leading people to question vaccines?

A: I dont study cultural and political drivers, so here are a few of my guesses. The level of misinformation and disinformation about vaccines and their safety seems like a huge problem. And as I referred to, the lack of access to health care and vaccines, particularly in low-income countries, is another huge problem. The drop in vaccination rates, where past successful vaccination campaigns have made once familiar diseases very rare, may also get at one of the paradoxes of public health: With a successful public health intervention, over time people forget about a diseases consequences and come to question the need to continue investing in the intervention.

We need to identify communities and populations where vaccination rates are decreasing or are low enough to warrant concern, so we can better understand the drivers at work and effectively respond to them. We need to counter disinformation, providing forums for trusted health advisors. And we need to redouble our global commitment to providing health careand in this case specifically, providing access to vaccinesfor all.

Maya Brownstein

Photos: iStock/Kittisak Kaewchalun; Kent Dayton

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Measles outbreaks show the risk of under-vaccination | News | Harvard T.H. Chan School of Public Health - HSPH News

Immunology

Spring Allergy Season Is Getting Worse. Here’s What to Know. – The New York Times

Spring is here and if youre among the estimated one in four adults in the United States who suffers from seasonal allergies, your sneezing and scratching may have already started.

With climate change affecting temperatures and plant growth, you may need to be on the lookout earlier than ever before. It can be hard to distinguish allergy symptoms from those of a cold, but experts point to a few telltale signs.

Spring allergy seasons are beginning about 20 days earlier than they had, according to an analysis of pollen count data from 60 stations across North America from 1990 to 2018.

That shift can have significant health consequences, said William Anderegg, who is an author of the study and an associate professor of biology at the University of Utah. Other research has shown that very early onset of spring is associated with higher prevalence of allergic rhinitis, also known as hay fever. When people end up sick or in the hospital from uncontrolled allergy symptoms, he said, its because they didnt expect it, and didnt have medications in hand.

The researchers also found that pollen concentrations have risen about 20 percent nationwide since 1990, with Texas and the Midwest having the greatest increases. Warmer temperatures, higher concentrations of carbon dioxide and increased precipitation can all contribute to plants growing bigger and producing more pollen over longer periods of time, Dr. Anderegg said.

Dr. Gailen Marshall, chair of the allergy and immunology department at the University of Mississippi Medical Center, said that when he began practicing nearly 40 years ago, allergy seasons were confined to about eight weeks each. Tree pollen hit in the spring, grass pollen increased in spring and summer and ragweed pollen picked up in late summer and early fall.

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Spring Allergy Season Is Getting Worse. Here's What to Know. - The New York Times

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

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

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

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