Latest news with #FredHutchinsonCancerCenter
Business Insider
14-07-2025
- Health
- Business Insider
A doctor who studies how a healthy gut can prevent colon cancer does 3 simple things to lower his risk
Colon cancer is rising in people under 50, and poor gut health could be part of the problem. Dr. Neelendu Dey studies whether gut microbes can be harnessed to prevent and treat colon cancer. To reduce his colon cancer risk, he eats lots of fiber and plays sports. More people under the age of 50 are getting colon cancer — but it's unclear why. A doctor who researches the link between the disease and our gut microbes has a theory. "I don't want to give the message that microbes are the entire thing. But we know that there are significant correlations between how much we have of various microbes and cancer," Dr. Neelendu Dey, an associate professor at Fred Hutchinson Cancer Center in Seattle, told Business Insider. Trillions of microbes live in our colon lining, and research suggests the more diverse they are the better our health and the lower our chances of developing diseases including colon and other forms of cancer, obesity, type 2 diabetes, and depression. What we eat and our environment affect the make-up of what's known as the gut microbiome, for instance, ultra-processed foods and being sedentary are thought to harm it. More young people are being diagnosed with colon cancer. Business Insider is telling their stories and helping readers understand how to prevent the disease and what could be causing the spike. If you would like to share your story or expertise, please contact Kim Schewitz: kschewitz@ Dey's lab researches how microbes could be used to prevent and treat colon cancer, but everyone's gut microbiome is unique, he said. By understanding how individual microboes respond to different ingredients, they hope to provide personalized dietary recommendations to prevent precancerous polyps from forming. Dey is 45, the age the American Cancer Society recommends those with an average risk of colon cancer start getting colonoscopies every 10 years. To lower his colon cancer risk, first and foremost, Dey said he follows official advice to get screened. Those at higher risk, for example, with a genetic predisposition, can talk to their doctor to decide if earlier screening is necessary. But Dey also makes diet and lifestyle choices to look after his gut microbiome, in the hopes of reducing his colon cancer risk. "The microbiome, I believe, is a long-term player in improving our health," he said. "Working with our microbiome is akin to, let's say, practicing the violin every day if you want to be a good violinist." 1) Eat fiber at every meal Dey tries to incorporate some fiber into each of his meals, because there is strong data to suggest they can boost gut health over time. Fiber is found in plant foods such as fruits, vegetables, nuts, beans, and oats, and it feeds the "good" bacteria in the gut. A 2018 study based on The American Gut Project analyzed the stool samples and eating habits of 10,000 people, and found that those who ate 30 types of plant foods a week had more diverse microbiomes than those who ate 10 or fewer. Being of South Asian descent, Dey often makes Indian dishes, many of which contain lentils, chickpeas, and spices. "Good" microbes don't all eat the same type of fiber. That's why the authors think eating lots of different types leads to a more diverse microbiome. 2) Avoiding ultra-processed foods Ultra-processed foods, which can range from foods such as protein bars to oven pizza, are made using ingredients you wouldn't find in a typical kitchen. They contain additives like emulsifiers and gums, often come in plastic packaging, and are designed to be hyperpalatable, making them easy to overeat. UPFs have been linked to a host of serious health problems, including colon cancer, but are ubiquitous in modern America. For this reason, Dey tries to avoid them when possible, but knows it's not realistic to cut them out entirely. "When I can control it, certainly I do. If I have the time, I would rather grab the apple than the processed bar that contains an apple," he said. 3) Exercising regularly Dey is part of a kickball team and exercises independently, too. He does this because, as well as boosting heart health and helping him maintain a healthy weight, working out is beneficial for gut health. Regular exercise can help food move through the digestive system more quickly, reducing the time the colon is exposed to toxins. Studies suggest that working out can also increase the number of "good" microbes in the gut, improving diversity. "Certainly, exercise — I find, and I think others find — has huge benefits for gut health," Dey said.
Medscape
08-07-2025
- Health
- Medscape
Waist Measure Improved Mortality Prediction in Older Women
By using waist circumference along with BMI, modest gains were made in predicting which postmenopausal women were at a higher risk for premature death, a prospective cohort study has found. While obesity remains a pressing public health threat, prevention and treatment are made difficult by the limits of the BMI to accurately measure excess adiposity, according to the study's authors. 'Waist circumference is a simple, inexpensive method to assess visceral adiposity and correlates well with visceral fat as assessed by imaging,' Aaron K. Aragaki, MS, and his colleagues wrote. Aragaki is a researcher at the Fred Hutchinson Cancer Center in Seattle. The problem, wrote Aragaki and his colleagues, is that waist circumference is not often measured in the clinical setting. Further, 'Waist circumference would be especially valuable for staging of obesity risk if BMI-specific thresholds were available,' they wrote. The investigators said that the current recommended waist circumference thresholds do not complement BMI because most adults diagnosed with obesity are already beyond these thresholds. Currently accepted waist circumference thresholds for overweight are 88 cm or above for women and 102 cm or above for men. To stratify risk more accurately, new BMI-specific waist circumference threshold recommendations have been made recently by the International Atherosclerosis Society (IAS) and the International Chair on Cardiometabolic Risk (ICCR) Working Group on Visceral Obesity. They have proposed thresholds in women of 80 cm or greater, 90 cm or greater, 105 cm or greater, 115 cm or greater, and 115 cm or greater to correlate, respectively, with BMI categories: normal weight (18.5 to < 25), overweight (25 to < 30), obesity 1 (30 to < 35), obesity 2 (35 to < 40), and obesity 3 (≥ 40). In men, they propose the corresponding waist measurements of 90 cm or greater, 100 cm or greater, 110 cm or greater, 125 cm or greater, and 125 cm or greater to correlate with the respective BMI categories. A consensus statement issued in 2020 by the IAS and the ICCR suggested that prospective data were needed to further stratify BMI categories by waist circumference thresholds to improve mortality risk prediction compared with BMI categories. To that end, Aragaki and his colleagues examined all-cause mortality data from the Women's Health Initiative (WHI), a large, national, multicenter, population-based study of generally healthy postmenopausal women (aged between 50 and 79 years), with enrollment from 1993 to 1998 and follow-up through 2021. Data of 139,213 women from the WHI were distributed across three groups. There was a development cohort (N = 67,774) and two validation cohorts, one according to overweight and obesity prevalence, and another according to geography and diversity. Validation Cohort 1 (N = 48,335) had half the prevalence of prior cardiovascular disease and cancer as the development group, but a higher rate of overweight or obesity (72.6% vs 59.1%). Validation Cohort 2 (N = 23,104) had nearly twice the number of women who identified as Black compared with the development group (12.7% vs 6.4%) and nearly three times the number of women who identified as Hispanic (9.1% vs 3.1%). Aragaki and his colleagues analyzed annual all-cause mortality in the datasets and the National Death Index. They found that respective death rates at 10- and 20-year follow-up marks were 5808 and 22,124 in the development cohort; 3418 and 14,252 in Validation Cohort 1, and 2123 and 7668 in Validation Cohort 2. Validation Cohort 1 had a higher prevalence of large waist circumference (21.9%) than Validation Cohort 2 (18.2%), according to currently accepted BMI-specific thresholds. Nearly all women with obesity 2 or obesity 3 had a waist circumference of 88 cm or larger, whereas women with a normal weight did not much exceed this waist circumference threshold. Differences in the percentage of trunk fat between women with normal waist circumference and those with large waist circumference within the same BMI categories across centers were notable, ranging from 0.5 to 1.0 SDs. Baseline risk for mortality at 10 and 20 years was highest in those with a prior history of disease and was lowest in those with no prior disease or preexisting condition across 5-year age groups, Aragaki and his colleagues found. All estimated hazard ratios in the mortality model were associated with higher mortality risk compared with the baseline risk. When BMI categories > 30 were added to this model, they were positively associated with higher mortality risk in a dose-dependent manner compared with the BMI category of normal weight. After stratification of BMI categories by waist circumference thresholds, hazard ratios were consistently greater for BMI categories with large waist circumference than their counterparts with normal ones. The mortality risk in women with normal weight or overweight and large waist circumferences was similar to that in women with obesity 1 and a normal waist circumference. Mortality risk in those with obesity 1 and a large waist circumference was similar to that in women with obesity 3 and normal waist circumference. Stratifying BMI categories by waist circumference thresholds improved mortality discrimination over BMI alone at 10 years for Validation Cohort 1, with the c-statistic increasing from 60.7% (95% CI, 59.5%-61.9%) to 61.3% (95% CI, 60.2%-62.5%), an improvement of 0.7% (95% CI, 0.3%-1.0%). The c-statistic is the agreement between the number of observed outcomes and predicted risk at 10 and 20 years, according to Aragaki and his colleagues. Discrimination was not significantly improved for Validation Cohort 2, however, with a difference in c-statistics of 0.3% (95% CI, 0.2%-0.7%). 'Combining BMI and waist circumference assessments allows for more personalized decision making,' Aragaki and his colleagues wrote. 'Patients with a large waist circumference in any BMI category are at elevated cardiometabolic and mortality risk and may benefit from more aggressive interventions than those with similar BMIs but lower waist circumferences. Conversely, those with a normal waist circumference may require less aggressive care.' The results of the study reinforce other data in favor of supplementing BMI with a second metric to more completely assess cardiometabolic health, a clinical obesity specialist told Medscape Medical News . 'BMI is a flawed criteria for diagnosis of obesity as it reflects total body mass but does not distinguish between fat and lean mass or where fat is distributed,' said Reema Hamid Dbouk, MD. 'Waist circumference is a surrogate for visceral fat, which is more metabolically active and linked to cardiometabolic risk and mortality.' Dbouk is an assistant professor of obesity medicine at Emory School of Medicine and a Rollins Distinguished Clinician at the Emory Clinic, both in Atlanta. 'Waist circumference measurement is inexpensive, quick, and requires minimal training. The paper notes that embarrassment or discomfort among patients is low, particularly among older adults. Integration into EMRs and vital sign protocols could normalize its use. Patients may understand waist size more intuitively than BMI. Tracking waist circumference over time may be more encouraging, especially if muscle gain masks fat loss on the scale,' said Dbouk. Dbouk said she thought the study was thorough, even if more data are still needed. 'Waist circumference-based thresholds may not fully account for differences in fat distribution by race/ethnicity or body habitus. For example, Asians may have higher metabolic risk at lower waist circumference. The thresholds are a step toward personalized risk assessment, but they may still require refinement to account for racial/ethnic differences in fat distribution and risk. More research is needed to validate waist circumference thresholds in broader populations, including men and younger individuals.'
Yahoo
11-06-2025
- Business
- Yahoo
Avidity Biosciences to Present Topline Data from Phase 1/2 FORTITUDE™ Trial of Del-brax in People Living with Facioscapulohumeral Muscular Dystrophy at 32nd Annual FSHD Society International Research Congress
-- FDA alignment on accelerated and full approval pathways for delpacibart braxlosiran (del-brax) in facioscapulohumeral muscular dystrophy (FSHD) -- -- Jeffrey M. Statland, M.D., Professor of Neurology, University of Kansas Medical Center, and FORTITUDE trial investigator, will present topline del-brax data from dose escalation cohorts in oral presentation -- -- Stephen Tapscott, M.D., Ph.D., Professor of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, will highlight results on the characterization of a novel DUX4-regulated circulating biomarker in oral and poster presentations -- SAN DIEGO, June 11, 2025 /PRNewswire/ -- Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company committed to delivering a new class of RNA therapeutics called Antibody Oligonucleotide Conjugates (AOCs™) to profoundly improve people's lives, today announced that the company will be presenting two oral and one poster presentations at the 32nd Annual FSHD Society International Research Congress, being held June 12-13, 2025, in Amsterdam, the Netherlands. Earlier this week, Avidity announced FDA alignment on accelerated and full approval pathways for delpacibart braxlosiran (del-brax) in facioscapulohumeral muscular dystrophy (FSHD). 32nd Annual FSHD Society International Research Congress Presentations Topline Data from Dose Escalation Cohorts A and B in FORTITUDE™, a Phase 1/2 Trial Evaluating Del-brax (delpacibart braxlosiran) in Adults with Facioscapulohumeral Muscular Dystrophy (FSHD) Oral presentation: Jeffrey M. Statland, M.D., to present June 13, 2025, from 5:20 - 5:40 p.m. Central European Summer Time (CEST) / 11:20 - 11:40 a.m. ET Characterization of a promising DUX4-regulated circulating biomarker for facioscapulohumeral dystrophy (FSHD) Oral presentation: Stephen Tapscott, M.D., Ph.D., Professor of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, to present on June 12, 2025, from 6:25 - 6:30 p.m. CEST / 12:25 - 12:30 p.m. ET Poster presentation (#7.08): June 12, 2025, from 7:15 - 8:00 p.m. CEST / 1:15 - 2:00 p.m. ET The presentations and poster are available on the publications page of Avidity's website at About AvidityAvidity Biosciences, Inc.'s mission is to profoundly improve people's lives by delivering a new class of RNA therapeutics - Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare neuromuscular diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is also advancing two wholly-owned precision cardiology development candidates addressing rare genetic cardiomyopathies. In addition, Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through key partnerships. Avidity is headquartered in San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit and engage with us on LinkedIn and X. Forward-Looking StatementsAvidity cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: Avidity's plans to present topline data from the dose escalation cohorts of the Phase 1/2 FORTITUDE™ trial; the status and availability of accelerated and full approval pathways for del-brax and Avidity's planned participation at the 32nd Annual FSHD Society International Research Congress and the contents of its scheduled presentations. The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of these plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Avidity's business and beyond its control, including, without limitation, the data and results produced from the clinical study of del-brax may not support BLA submission or accelerated or full approval, and may not be satisfactory to the FDA and other regulators; later developments with the FDA and other regulators may be inconsistent with the feedback received as of the date hereof; and the risks described in Avidity's Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and subsequent filings with the SEC. Avidity cautions readers not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that arise after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investor Contact:Kat Lange(619) 837-5014investors@ Media Contact:Kristina Coppola (619) 837-5016media@ View original content to download multimedia: SOURCE Avidity Biosciences, Inc. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
31-05-2025
- Health
- Yahoo
HIV's Most Promising Breakthrough Has Taken a Hit
Solving HIV vaccination—a puzzle that scientists have been tackling for decades without success—could be like cracking the code to a safe. The key, they now think, may be delivering a series of different shots in a specific sequence, iteratively training the body to produce a strong, broad immune response that will endure against the fast-mutating virus, ideally for a lifetime. Figuring out which ingredients to include in those shots, and in which order, is one of the trickiest immunological conundrums that researchers have ever faced. But mRNA, the fast, flexible technology that delivered two of the world's first COVID-19 vaccines in record time, is ideal for that kind of brute-force tinkering, and may be the most important tool for getting an effective HIV vaccine, Julie McElrath, the head of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center, in Seattle, told me. Multiple mRNA-based HIV vaccines are now in clinical trials, and early data suggest that they're prompting the type of immune responses that researchers think are essential to keeping HIV at bay—and that other vaccine candidates have struggled to elicit at all. But recently, several promising mRNA HIV-vaccine candidates have slammed up against a technical roadblock. In two small clinical trials, 7 to 18 percent of participants developed rashes and other skin reactions after getting the shots—including multiple cases of chronic hives that troubled volunteers for months after they were immunized. All of the vaccines were manufactured by Moderna. The rashes aren't life-threatening; they're also readily treatable. Still, they can be debilitating and distressing. 'I've had patients who literally can't go to work,' Kimberly Blumenthal, an allergist and immunologist at Massachusetts General Hospital, who has treated people with chronic hives, told me. The rate at which they're occurring in the trials is also out of the norm, and no one has an explanation yet for the root cause. To prioritize patient safety, mRNA HIV-vaccine research in people has slowed as researchers try to suss out the cause of the hives, William Schief, the Scripps Research Institute biophysicist who helped design one of the vaccines, told me. (Schief also holds titles at Moderna and at IAVI, the nonprofit that sponsored some of the HIV-vaccine work.) At any time, a side effect this uncomfortable and prolonged would give researchers pause. But in 2025, a setback for a high-profile mRNA vaccine trial—focused on HIV, no less—could more fundamentally upend potentially lifesaving research. Secretary of Health and Human Services Robert F. Kennedy Jr., a longtime and prominent anti-vaccine activist, has repeatedly questioned the safety of mRNA COVID vaccines. He and agency leaders are already recommending that fewer Americans take vaccines and creating new hurdles to vaccine approval. Since January, the National Institutes of Health, under HHS's direction, has also terminated funding for hundreds of research projects related to HIV and vaccines. This week, the department canceled Moderna's nearly $600 million contract to develop mRNA-based flu vaccines. The HIV-vaccine studies that detected the skin reactions were also supported by NIH funding, and the researchers involved collaborated directly with NIH scientists. But those partnerships have since been terminated, and the NIH is now telling several agency-supported researchers working on HIV vaccines that the government is not planning to continue funding their work, according to several researchers I talked with. When reached for comment, Emily Hilliard, HHS's press secretary, wrote in an email, 'The reality is that mRNA technology remains under-tested, and we are not going to spend taxpayer dollars repeating the mistakes of the last administration, which concealed legitimate safety concerns from the public'—referencing the mRNA-based COVID-19 vaccines, which were rigorously tested in clinical trials, and billions of doses of which have been safely administered people around the world. Under normal circumstances, detecting rashes in a small vaccine-safety study would represent a routine scientific setback, and prove that the trials served their intended purpose. But the administration's anti-vaccine stances have created a culture of fear among scientists: Several of the researchers I contacted for this story declined to comment, for fear of publicly tying their name or institution to reporting on mRNA vaccines and losing funding for their research. Science requires resources and open discussion—in torpedoing both, the Trump administration is rapidly undoing decades of progress toward ending the HIV pandemic. Researchers running the mRNA HIV-vaccine trials first took note of the rashes in 2022, shortly after studies began. After Science magazine reported about the side effect connected with the IAVI-sponsored vaccine, many scientists in the field weren't sure what to make of the finding. The trial in which it had been reported had enrolled only 60 people, and it wasn't set up to rigorously look at a mysterious side effect. 'The sort of feeling was, Yeah, that's a bit weird, God knows what happened,' John Moore, an HIV researcher and vaccinologist at Cornell, told me. This April and May, though, researchers independently published two papers describing the rashes, for four separate vaccines, in two separate trials: one for the IAVI-backed vaccine and another run by the HIV Vaccine Trials Network. Now, the side effect is 'real, confirmed, generalizable,' Moore said. 'And we don't know why it's happening.' The vaccines in question target slightly different parts of the virus. But all of them rely on a Moderna-manufactured mRNA backbone, and all of them triggered, in up to about 10 percent of participants, chronic hives that emerged a few days or weeks after vaccination and in many cases lasted for months. That's a long time to be battling itching and discomfort—and it threatens to be a major deterrent to completing the series of vaccines, or potentially starting at all, Genevieve Fouda, an immunologist and HIV researcher at Cornell, told me. Delayed, chronic hives have long been known as a rare side effect of vaccines, including mRNA-based COVID vaccines. But the rates are generally very low—usually well under 1 percent, and often detectable only in massive studies of thousands of people. To see these rashes crop up in two small safety studies—one of 60 people, the other of 108—is a significant departure from precedent, scientists told me. And working out why they're appearing at such high rates will take time. Although researchers understand that the reactions are a kind of autoimmunity—in which the body inadvertently learns to attack itself—they don't know exactly why rashes occur after certain immunizations or infections, Blumenthal told me. In this case, the data so far do point to the specific combination of mRNA and HIV as a root cause. Other mRNA vaccines, including Moderna's, haven't had this issue to anywhere near this degree; neither have other HIV vaccines that have made it into people. And several researchers pointed out to me that, so far, the only trials that they're aware of in which these hives have turned up at this frequency have involved a Moderna-manufactured product. None of the other vaccines being tested by the HIV Vaccine Trials Network, for instance, has seen rashes at that rate—including other, non-Moderna mRNA HIV vaccines, Jim Kublin, the director of HVTN, told me. (Barton Haynes, the Duke immunologist leading work on one of the non-Moderna vaccines, told me he and his colleagues have not encountered the same skin-reaction problem.) Hives also appear to have been a more common side effect of the Moderna COVID vaccines than of the Pfizer ones, though still overall rare. 'This is truly an outlier in terms of what we've seen,' Robert Paris, a vice president at Moderna, told me. A persistent mRNA problem would be a major blow to HIV-vaccine development. When the technology emerged, it sped progress like nothing else: 'Things that originally took us about three years, we could do them in maybe three and a half months or so,' Mark Feinberg, the head of IAVI, told me. The early results for these vaccines have also been very promising, and before the hives were detected, researchers were well on their way to testing even more iterations of mRNA-based HIV vaccines, to crack the final immunization code. But for the moment, 'there's no appetite to say, 'Let's try all these different immunogens and see what happens,'' Schief, the Scripps researcher who helped design one of the vaccines, told me. Still, most of the researchers I spoke with insisted that they'll find a solution soon. The mRNA vaccines for HIV 'are not at all dead in the water,' Kublin told me. If needed, scientists could tweak the vaccine recipe, or combine the mRNA approach with another technology. The fix may be as simple as lowering the vaccine dose, a strategy that Schief and Feinberg are working to test in a new trial based in South Africa. (Moderna's COVID vaccine also contained more than three times as much mRNA as Pfizer's—and one study found that lowering the Moderna dose seemed to reduce the rate of certain skin reactions.) Successful HIV vaccination may require a balancing act—minimizing hives, while still delivering enough mRNA to rile up the immune system. But researchers may not be able to drive the rates of skin reactions down to zero: HIV is especially adept at cloaking itself from the immune system, and there may be few ways to force the body to attack the virus without producing collateral damage. And Schief and others couldn't say what rate of hives would be acceptably low. The virus is so infectious and deadly that some minor side effects may be worth the risk, if the vaccine is effective at generating the right immune response. But even a perfect, immunity-inducing shot won't do the world any good if people are afraid to take it. Still, if a rash can dissuade someone from vaccination, so, too, can misinformation, or an official's decision to stop recommending a shot. No vaccine progress will be made if the federal government doesn't want it to happen: Paris, of Moderna, told me that earlier this spring, the NIH terminated its partnership with the researchers developing these mRNA HIV vaccines, forcing the scientists to seek alternate sources of support. And yesterday, Schief and Haynes were told that their groups at Scripps and Duke would not have the opportunity to renew funding for the two HIV-vaccine-focused research consortia that their institutions lead—millions of dollars that the researchers had been told to expect they would receive, and that have been powering the development of their mRNA shots. The rationale, Haynes told me, as it was described to him, was 'due to the desire to go with currently available approaches to eliminate HIV.' Currently available approaches include community education and preventive drugs, but notably, no vaccine. (HHS did not respond to questions about these funding shifts.) 'Unless we can find a substitute source of support, this work won't go forward,' Haynes told me. If the project of HIV vaccination looks less promising right now than it has in years, that's not about science or technology, or about any single side effect: It's about politics. Article originally published at The Atlantic
Atlantic
31-05-2025
- Health
- Atlantic
HIV's Most Promising Breakthrough Has Taken a Hit
Solving HIV vaccination—a puzzle that scientists have been tackling for decades without success—could be like cracking the code to a safe. The key, they now think, may be delivering a series of different shots in a specific sequence, iteratively training the body to produce a strong, broad immune response that will endure against the fast-mutating virus, ideally for a lifetime. Figuring out which ingredients to include in those shots, and in which order, is one of the trickiest immunological conundrums that researchers have ever faced. But mRNA, the fast, flexible technology that delivered two of the world's first COVID-19 vaccines in record time, is ideal for that kind of brute-force tinkering, and may be the most important tool for getting an effective HIV vaccine, Julie McElrath, the head of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center, in Seattle, told me. Multiple mRNA-based HIV vaccines are now in clinical trials, and early data suggest that they're prompting the type of immune responses that researchers think are essential to keeping HIV at bay—and that other vaccine candidates have struggled to elicit at all. But recently, several promising mRNA HIV-vaccine candidates have slammed up against a technical roadblock. In two small clinical trials, 7 to 18 percent of participants developed rashes and other skin reactions after getting the shots—including multiple cases of chronic hives that troubled volunteers for months after they were immunized. All of the vaccines were manufactured by Moderna. The rashes aren't life threatening; they're also readily treatable. Still, they can be debilitating and distressing. 'I've had patients who literally can't go to work,' Kimberly Blumenthal, an allergist and immunologist at Massachusetts General Hospital, who has treated people with chronic hives, told me. The rate at which they're occurring in the trials is also out of the norm, and no one has an explanation yet for the root cause. To prioritize patient safety, mRNA HIV-vaccine research in people has slowed as researchers try to suss out the cause of the hives, William Schief, the Scripps Research Institute biophysicist who helped design one of the vaccines, told me. (Schief also holds titles at Moderna and at IAVI, the nonprofit that sponsored some of the HIV-vaccine work.) At any time, a side effect this uncomfortable and prolonged would give researchers pause. But in 2025, a setback for a high-profile mRNA vaccine trial—focused on HIV, no less—could more fundamentally upend potentially lifesaving research. Secretary of Health and Human Services Robert F. Kennedy Jr., a longtime and prominent anti-vaccine activist, has repeatedly questioned the safety of mRNA COVID vaccines. He and agency leaders are already recommending that fewer Americans take vaccines and creating new hurdles to vaccine approval. Since January, the National Institutes of Health, under HHS's direction, has also terminated funding for hundreds of research projects related to HIV and vaccines. This week, the department canceled Moderna's nearly $600 million contract to develop mRNA-based flu vaccines. The HIV-vaccine studies that detected the skin reactions were also supported by NIH funding, and the researchers involved collaborated directly with NIH scientists. But those partnerships have since been terminated, and the NIH is now telling several agency-supported researchers working on HIV vaccines that the government is not planning to continue funding their work, according to several researchers I talked to. When reached for comment, Emily Hilliard, HHS's press secretary, wrote in an email, 'The reality is that mRNA technology remains under-tested, and we are not going to spend taxpayer dollars repeating the mistakes of the last administration, which concealed legitimate safety concerns from the public'—referencing the mRNA-based COVID-19 vaccines, which were rigorously tested in clinical trials, and billions of doses of which have been safely administered people around the world. Under normal circumstances, detecting rashes in a small vaccine safety study would represent a routine scientific setback, and prove that the trials served their intended purpose. But the administration's anti-vaccine stances have created a culture of fear among scientists: Several of the researchers I contacted for this story declined to comment, for fear of publicly tying their name or institution to reporting on mRNA vaccines and losing funding for their research. Science requires resources and open discussion—in torpedoing both, the Trump administration is rapidly undoing decades of progress toward ending the HIV pandemic. Researchers running the mRNA HIV-vaccine trials first took note of the rashes in 2022, shortly after studies began. After Science magazine reported about the side effect connected with the IAVI-sponsored vaccine, many scientists in the field weren't sure what to make of the finding. The trial in which it had been reported had enrolled only 60 people, and wasn't set up to rigorously look at a mysterious side effect. 'The sort of feeling was, Yeah, that's a bit weird, god knows what happened,' John Moore, an HIV researcher and vaccinologist at Cornell, told me. This April and May, though, researchers independently published two papers describing the rashes, for four separate vaccines, in two separate trials: one for the IAVI-backed vaccine and another run by the HIV Vaccine Trials Network. Now, the side effect is 'real, confirmed, generalizable,' Moore said. 'And we don't know why it's happening.' The vaccines in question target slightly different parts of the virus. But all of them rely on a Moderna-manufactured mRNA backbone, and all of them triggered, in up to about 10 percent of participants, chronic hives that emerged a few days or weeks after vaccination and in many cases lasted for months. That's a long time to be battling itching and discomfort—and it threatens to be a major deterrent to completing the series of vaccines, or potentially starting at all, Genevieve Fouda, an immunologist and HIV researcher at Cornell, told me. Delayed, chronic hives have long been known as a rare side effect of vaccines, including mRNA-based COVID vaccines. But the rates are generally very low —usually well under 1 percent, and often detectable only in massive studies of thousands of people. To see these rashes crop up in two small safety studies—one of 60 people, the other of 108—is a significant departure from precedent, scientists told me. And working out why they're appearing at such high rates will take time. Although researchers understand that the reactions are a kind of autoimmunity—in which the body inadvertently learns to attack itself—they don't know exactly why rashes occur after certain immunizations or infections, Blumenthal told me. In this case, the data so far do point to the specific combination of mRNA and HIV as a root cause. Other mRNA vaccines, including Moderna's, haven't had this issue, to anywhere near this degree; neither have other HIV vaccines that have made it into people. And several researchers pointed out to me that, so far, the only trials that they're aware of in which these hives have turned up at this frequency have involved a Moderna-manufactured product. None of the other vaccines being tested by the HIV Vaccine Trials Network, for instance, has seen rashes at that rate—including other, non-Moderna mRNA HIV vaccines, Jim Kublin, the director of HVTN, told me. (Barton Haynes, the Duke immunologist leading work on one of the non-Moderna vaccines, told me he and his colleagues have not encountered the same skin-reaction problem.) Hives also appear to have been a more common side effect of the Moderna COVID vaccines than of the Pfizer ones, though still overall rare. 'This is truly an outlier in terms of what we've seen,' Robert Paris, a vice president at Moderna, told me. A persistent mRNA problem would be a major blow to HIV-vaccine development. When the technology emerged, it sped progress like nothing else: 'Things that originally took us about three years, we could do them in maybe three and a half months or so,' Mark Feinberg, the head of IAVI, told me. The early results for these vaccines have also been very promising, and before the hives were detected, researchers were well on their way to testing even more iterations of mRNA-based HIV vaccines, to crack the final immunization code. But for the moment, 'there's no appetite to say, 'Let's try all these different immunogens and see what happens,'' Schief, the Scripps researcher who helped design one of the vaccines, told me. Still, most of the researchers I spoke with insisted that they'll find a solution soon. mRNA vaccines for HIV 'are not at all dead in the water,' Kublin told me. If needed, scientists could tweak the vaccine recipe, or combine the mRNA approach with another technology. The fix may be as simple as lowering the vaccine dose, a strategy that Schief and Feinberg are working to test a new trial based in South Africa. (Moderna's COVID vaccine also contained more than three times as much mRNA as Pfizer's—and one study found that lowering the Moderna dose seemed to reduce the rate of certain skin reactions.) Successful HIV vaccination may require a balancing act—minimizing hives, while still delivering enough mRNA to rile up the immune system. But researchers may not be able to drive the rates of skin reactions down to zero: HIV is especially adept at cloaking itself from the immune system, and there may be few ways to force the body to attack the virus without producing collateral damage. And Schief and others couldn't say what rate of hives would be acceptably low. The virus is so infectious and deadly that some minor side effects may be worth the risk, if the vaccine is effective at generating the right immune response. But even a perfect, immunity-inducing shot won't do the world any good if people are afraid to take it. Still, if a rash can dissuade someone from vaccination, so, too, can misinformation, or an official's decision to stop recommending a shot. No vaccine progress will be made if the federal government doesn't want it to happen: Paris, of Moderna, told me that earlier this spring, the NIH terminated its partnership with the researchers developing these mRNA HIV vaccines, forcing the scientists to seek alternate sources of support. And yesterday, Schief and Haynes were told that their groups at Scripps and Duke would not have the opportunity to renew funding for the two HIV-vaccine-focused research consortia that their institutions lead—millions of dollars that the researchers had been told to expect they would receive, and that have been powering the development of their mRNA shots. The rationale, Haynes told me, as it was described to him, was 'due to the desire to go with currently available approaches to eliminate HIV.' Currently available approaches include community education and preventive drugs, but notably, no vaccine. (HHS did not respond to questions about these funding shifts.) 'Unless we can find a substitute source of support, this work won't go forward,' Haynes told me. If the project of HIV vaccination looks less promising right now than it has in years, that's not about science or technology, or about any single side effect: It's about politics.
