Latest news with #KimberlyBlumenthal
Yahoo
3 days ago
- 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
3 days ago
- 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.
Medscape
12-05-2025
- Health
- Medscape
Reversing Inaccurate Penicillin Allergy Labeling
Accurate labeling of penicillin allergies is essential, but unconfirmed penicillin allergies may have negative effects on individual and public health, according to experts. A trend toward 'de-labeling' by testing individuals with documented penicillin allergies is gaining steam, in part as a way to reduce antibiotic use and curb the emergence of more resistant bacteria, according to Upeka Samarakoon, PhD, of Massachusetts General Hospital, Boston, and colleagues in a review article published in 2023 in the Annals of Allergy, Asthma, and Immunology . The article outlined the benefits of de-labeling and identified how patients are labeled with a penicillin allergy. Individuals acquire a penicillin allergy label either by reporting a past reaction to penicillin or displaying a reaction recorded by a healthcare provider. Removing the allergy label from a patient's medical record may involve an evaluation of reaction history and often following an in-office drug challenge, according to the authors. Why Lose the Label? Penicillin antibiotics are first-line treatments for infections commonly treated in primary care settings — strep throat, ear infections, and urinary tract infections, said Kimberly G. Blumenthal, MD, the corresponding author of the review article, in an interview. 'Inaccurate penicillin allergy labels lead to inferior clinical outcomes from using second- line treatments, which are often broad-spectrum antibiotics,' said Blumenthal, an allergist/immunologist and clinical researcher at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, Boston. 'Patients with unconfirmed penicillin allergy labels have an increased risk of treatment failures, healthcare-associated infections, and colonization or infection with resistant organisms,' she added. Proactively de-labeling patients with unverified penicillin allergies will improve their future care as they will be able to receive first-line treatments in times of need, said Blumenthal. 'Awareness of the importance of penicillin allergy de-labeling does seem to be increasing in primary care, but barriers exist for implementing de-labeling practices outside of allergy specialist clinics,' Blumenthal told Medscape Medical News . More work is needed to increase penicillin allergy de-labeling by generalists, potentially through the use of electronic health records or other decision tools and algorithms to assess patients, she said. Barriers to increased de-labeling in primary care include limited time, productivity targets, and pressure to achieve quality metrics for chronic health diseases, Blumenthal said. 'Additionally, primary care physicians report that they lack allergy knowledge and lack the resources needed for penicillin allergy evaluations,' she said. 'Potential solutions to these barriers include having a dedicated penicillin allergy de-labeling clinic, including questions on penicillin allergies during annual visits, and increasing education related to penicillin allergy de-labeling for generalists,' Blumenthal noted. Clinician's Guide to De-Labeling The use of simple allergy history tools can go a long way toward de-labeling a penicillin allergy, Blumenthal told Medscape Medical News . 'Many penicillin allergy labels lack a reaction or should not be there at all and warrant de-labeling based on history alone,' she said. For example, a patient who has subsequently taken penicillin with no reaction or had only a family history of penicillin allergy is a candidate for de-labeling, she said. For individuals who may have an allergy, risk stratification tools such as PEN-FAST can identify low-risk patients who are suitable for de-labeling in primary care, Blumenthal said. 'A patient with a PEN-FAST score of 0, in my opinion, would be appropriate for primary care de-labeling in the US. Higher-risk patients can be referred to allergy specialists,' she added. The 2023 article contains a more detailed explanation of the de-labeling process, which can be done in a few hours' time and at relatively low cost, according to the authors. Safely Ruling Out the Allergy The majority of patients who are labeled as allergic to penicillin are, in fact, not allergic, said John Kelso, MD, in a presentation on allergies at the annual meeting of the American College of Physicians (ACP), previously reported by Medscape Medical News . Patients labeled as penicillin-allergic but who have no history of severe cutaneous adverse reactions are candidates for de-labeling, Kelso said. 'Many patients go through their entire lives unable to receive the best treatment for infections because they are mislabeled as being allergic to penicillin,' he emphasized. An intradermal skin test can confirm or rule out a penicillin allergy for patients who experienced hives after a first dose of a new course of penicillin, but blood tests are not reliable, Kelso said in his ACP presentation. De-labeling has increased dramatically in the last few years, both in allergist offices and in primary care settings, driven in part by campaigns from the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; the Centers for Disease Control and Prevention; and the Infectious Diseases Society of America, Kelso told Medscape Medical News . Clinicians often assume that the process of de-labeling a penicillin allergy is 'complicated, time-consuming, and dangerous,' but that is not the case, Kelso said. To begin the de-labeling process, screen patients with appropriate questions to exclude those whose prior reaction may have been immediate anaphylaxis or a late-onset severe cutaneous adverse reaction, Kelso said in an interview. Once such patients are excluded, the process simply involves administration of a dose of amoxicillin followed by a 1-hour observation period in the clinic and asking the patients to report any late onset reactions that might develop over the next day or two, he said. A large body of research exists to support de-labeling of penicillin allergies, Kelso told Medscape Medical News . 'Perhaps the most important finding is that 95% of patients who are labeled as being allergic to penicillin are not, either because the original reaction was coincidental or the allergy has been lost over time; thus, the vast majority of patients who undergo an amoxicillin challenge for penicillin de-labeling will do so uneventfully,' he noted. 'Once an appropriate history has been taken to exclude the patients who may be at risk of a more severe reaction, the remainder should be offered the de-labeling by amoxicillin challenge so that in the future they can offered the most appropriate treatment,' he said.
