For the first time, researchers have found a potential drug candidate that improved outcomes for patients with a type of childhood brain tumor for which there are no effective treatments. The compound, called ONC201, nearly doubled survival for patients with diffuse midline glioma (DMG) or diffuse intrinsic pontine glioma (DIPG), compared to previous patients.

The findings are reported by an international team of researcher led by the University of Michigan Health Rogel Cancer Center and the Chad Carr Pediatric Brain Tumor Center.

In addition to reporting on the results of two early stage clinical trials, the paper reveals the underlying mechanisms behind the compound's success in these tumors. The paper is published in Cancer Discovery, a journal of the American Association for Cancer Research.

Diffuse midline gliomas including DIPG with a mutation called H3K27M are particularly aggressive, with an overall survival rate of 11-15 months. These tumors are most frequently found in children and young adults. The only available treatment is radiation, and even that is difficult as the tumors are located amid brain regions with critical functions.

"It's an incredibly difficult tumor to treat," said senior author Carl Koschmann, M.D., associate professor of pediatric neuro-oncology and clinical scientific director of the Chad Carr Pediatric Brain Tumor Center at Michigan Medicine. "Prior to this study, there have been more than 250 clinical trials that have not been able to Improve outcomes. This is a major crack in the armor."

In two clinical trials testing ONC201 in a total of 71 patients with H3K27M-mutated diffuse midline gliomas, the median overall survival was nearly 22 months for tumors that had not recurred at the time of enrollment. Almost a third of the patients lived longer than two years.

ONC201 took an unusual path to a clinical trial. Initially designed to target dopamine receptors, which are upregulated in many different tumors, researchers saw that the drug passes the blood-brain barrier, one of the biggest challenges to designing drugs for brain tumors. Initial trials in glioblastoma were not successful, but a small number of patients with DMG that carried the H3K27M mutation had more promising results. Without understanding why it worked better in these patients, a phase 1 trial was started in children and young adults with H3K27M-mutated DMG.

Meanwhile, Koschmann and co-author Sriram Venneti, M.D., Ph.D., were trying to figure out what was happening in these tumor cells.

Through the trial, they collected cerebrospinal fluid from patients. They used this fluid to analyze metabolic changes and found ONC201 got into the tumor cells and affected mitochondria. Patients who responded to the drug had an increase in a metabolite called L-2HG produced by tumor cells.

Koschmann called the finding "very much unexpected." The team found that increased L-2HG reversed tumor defining epigenetic signals causing tumor cells to differentiate more and divide less. The longer patients were on ONC201, the more tumors exhibited these epigenetic reversals.

"This could explain why this patient population was responding so well to the drug, because it had this specific epigenetic abnormality that could be turned off by ONC201. The tumors have an epigenetic change caused by the H3K27M mutation and ONC201 metabolically undoes that change," said Venneti, associate professor of pathology and pediatrics and scientific research director of the Chad Carr Pediatric Brain Tumor Center at Michigan Medicine.

Additional clinical trials are currently underway, including testing ONC201 in combination with other therapies. Researchers at U-M's Chad Carr Pediatric Brain Tumor Center are also continuing to look at ways to overcome resistance to ONC201 by using drug combinations.

Koschmann notes that even a near-doubling of survival is not enough for families of patients with this diagnosis, as the tumor remains very lethal. But he hopes this first step will lead to bigger leaps in the future.

"For now we have this patient population that didn't have a drug before, and now we see many of the tumors responding. We have a platform to build on and we can also explain why it's working," he said.

"We are really excited about this study and envision ONC201 becoming standard of care for these patients in the near future," Venneti said.

Jul 27 2023

Osivax, a biopharmaceutical company developing vaccines to provide broad-spectrum protection against highly mutating infectious viruses, today announced that The Lancet Infectious Diseases published results from the company's OVX836-003 study under the title, "Immunogenicity, safety and preliminary efficacy evaluation of OVX836, a nucleoprotein-based universal influenza A vaccine candidate: randomized, double-blind placebo-controlled, Phase 2a trial." The research article presents results of the study evaluating the safety and immunogenicity of OVX836, a broad-spectrum influenza vaccine, at three dose levels in healthy adults (NCT05060887). An efficacy assessment of OVX836 was also planned as an exploratory endpoint. The publication can be accessed at the following link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00351-1/fulltext.

Applying Osivax' proprietary oligoDOM^® technology platform, OVX836 is designed to target the nucleoprotein (NP), a highly conserved internal antigen. Unlike surface antigens, the NP is much less likely to mutate, alleviating the need for annual vaccination updates. OligoDOM^® enables the transformation of the NP into a highly immunogenic antigen to trigger powerful T-cell immune responses.

In the OVX836-003 study, a total of 137 healthy subjects aged 18-55 years received one intramuscular injection of the study vaccine or placebo as follows: 33 received OVX836 180 μg, 35 received OVX836 300 μg, 36 received OVX836 480 μg and 33 received a placebo. The OVX836 vaccine was safe and immunogenic at all dose levels. OVX836 elicited significant humoral and cellular NP-specific immune responses, including CD4⁺ and CD8⁺ T-cells. Most of the immunological markers (anti-NP IgG, NP-specific IFNγ SFCs, NP-specific CD4⁺ T-cells) showed a dose-dependent response from 180 µg to 480 µg. Induction of a measurable CD8⁺ response against a non-adjuvanted recombinant protein vaccine is challenging in humans and rarely reported, thus warranting the further evaluation of OVX836 in larger Phase 2b/3 clinical trials. Importantly, OVX836 provided an 84% level of protection against PCR-confirmed symptomatic influenza compared to placebo.

A separate cohort of 100 older adults (65 years old and older) was vaccinated (same doses and randomization ratio as younger subjects) and will be reported separately, with full results expected by Q4 2023.

"The favorable safety profile, and strong dose-dependent immune responses observed in this study underscore the potential of OVX836 as a promising influenza vaccine," commented Isabel Leroux-Roels, PhD, Principal Investigator at the Center for Vaccinology (CEVAC). "Notably, the observed signal of protection appears to be in line with the universal influenza vaccine target product profile set by the US National Institutes of Health, which is highly encouraging and certainly warrants closer evaluation in additional clinical trials."

"The publication of our Phase 2a data in the highly estimated Lancet ID journal is a significant appreciation and recognition of the robust nature of our study results," added Alexandre Le Vert, CEO and Co-Founder of Osivax. "We are strongly encouraged by these findings, particularly given that very few vaccine candidates pursuing a T-cell mechanism of action targeting the NP have elicited vaccine efficacy at this point in time. As such, we look forward to advancing OVX836 toward the next stages of clinical development as a truly universal influenza vaccine."

This article was originally published on Undark.

For as long as he can remember, Ken Pressey has had severe allergies to cats. They would trigger hives, runny nose, and watery eyes. Still, like many of the tens of millions of people in the United States who suffer from allergies, Pressey for years did not bother getting treated, or even diagnosed. When cats came near, he just avoided them. 

But that tactic has gotten tougher. During the pandemic, Pressey started dating a woman he’s now engaged to marry—and she has two cats. Being with the cats “was absolute chaos,” said the 30-year-old, who lives in Seattle. “I started having asthma attacks.”

Pressey’s primary care physician suggested allergy shots. This century-old approach, a form of immunotherapy, works by exposing the body to small, increasing doses of the culprit substance. Unlike over-the-counter pills and nasal sprays, which only relieve symptoms, shots address the root cause: They help the body build long-term tolerance to the allergens. The treatment is not a cure, but experts say it can bring relief in around 85 percent of patients who try it. And it’s not just a matter of curbing some sneezing. Beyond springtime sniffles, allergies make it hard to concentrate, leading to missed work and school. They can also disrupt sleep, trigger asthma, and contribute to mood disorders.

The procedure for alleviating this misery with allergy shots requires time and diligence. Typically, patients need injections once or twice a week for the first three to six months, then monthly jabs for three to five years. Each office visit also requires a half hour of monitoring after the shot in case of serious reactions, such as wheezing or throat swelling, which are rare but need immediate attention if they occur.

With these scheduling demands, allergy shots were a no-go for Pressey, an engineer with the United States Merchant Marines who often works overseas for months at a time. “I would not be able to keep up,” he said. While looking into alternatives, he recalled a conversation about allergy treatments while stationed in Europe several years earlier, when he heard a coworker say, “We do allergy drops. We don’t do shots. Why would you want to get stabbed by a needle?”

His colleague was referring to a form of sublingual immunotherapy, or SLIT, which builds immune tolerance to allergens administered daily under the tongue. The drops are formulated using the same liquid extracts in skin-based allergy tests, and research suggests the approach works—and is safe for patients to do at home. SLIT drops are a mainstay in Europe, Canada, and Latin America. In the United States, although some medical providers offer the drops off-label, prescribing the treatment remains limited for complex reasons related to regulatory purview and clinic revenue.

That means accessing SLIT drops can be tricky, even for highly motivated patients. “I did quite a bit of extensive reading,” Pressey said. The hardest part, he added, was finding a SLIT provider. Although he managed to connect with several doctors who offer the drops, their clinics were far away. Eventually Pressey went to a forum for allergies on Reddit, which led him to try a consult with Curex, one of more than a half dozen virtual health companies that have started selling allergy tests and SLIT directly to consumers.

Some of these companies launched during the pandemic when telehealth was rising and Covid concerns kept some allergy sufferers from going to clinic to get shots. The companies’ services focus on diagnosis and treatment of environmental allergies such as pets, dust, pollens, and grasses.

As more health services move online, patients have greater access to treatments but often sacrifice the continuity of traditional physician-patient relationships. As with other areas of medicine, finding allergy care has become a buyer-beware dilemma: Financial incentives and legal complications prevent SLIT from going mainstream with allergists, and so the challenge of making this treatment available and cost-effective has largely landed in the hands of non-allergist practitioners and business executives.

Allergen immunotherapy traces its roots to a pioneering experiment published in 1911. In that study, a pair of young British researchers rounded up patients and showed that injecting their arms with grass pollen toxins could calm their hay fever—which the researchers measured by dripping pollen extract into the patients’ eyes and noting the extent of burning and itching. With little understanding of the cells and molecules involved, physicians refined this method and, in 1954, confirmed its benefits in a double-blind trial. 

As the shots regimen gained popularity with physicians, the procedure proved quite safe overall, but news of several patient deaths in the early 1980s led some researchers to explore other ways to treat allergies without injections. Their efforts gave rise to sublingual immunotherapy—the liquid drops now offered by direct-to-consumer companies—and, initially, otolaryngologists, or ear, nose, and throat specialists saw potential in what appeared to be a gentler, more convenient allergy treatment.

Otolaryngology is primarily a surgical specialty. But allergies lie at the root of some of the complications that ENT physicians treat, and often present a roadblock. Whenever allergies cropped up as an underlying cause for his patients’ polyps and nasal disease, they “would never go for allergy therapy because, you know, it was always just shots,” said Chris Thompson, an ENT-trained head and neck surgeon in Austin, Texas, who opened his practice in 1997. 

Over the next decade, research continued on sublingual immunotherapy. By 2007, there was “growing consensus that specific sublingual immunotherapy (SLIT) does actually work,” according to one review in the Journal of Allergy and Clinical Immunology. In a 2009 position paper, the World Allergy Organization acknowledged SLIT as a viable treatment. Enterprising doctors began offering this type of immunotherapy.

Still, key details about the technique, such as what doses are needed to achieve benefit, seemed murky. “You could literally go to one doctor and get something that was 10,000 times weaker than what you might get from another doctor,” Thompson said. “There was no standardization.” 

Allergists were intrigued by sublingual therapy, but very few at the time offered it in clinic. According to a 2007 survey by the American College of Allergy, Asthma, and Immunology, just 5.9 percent of practicing allergists said they were using SLIT, and by 2011 that figure had only edged up to 11.4 percent. Most respondents cited the lack of FDA-approved products as a barrier.

Nevertheless, interest in sublingual immunotherapy grew in the ENT realm. Professional societies included symposiums about SLIT at their annual meetings and formed subgroups devoted to this new approach. Some otolaryngology group meetings offer courses for physicians to get started with SLIT, Thompson said.

Thompson watched the field a while, noting SLIT’s research progress amid overall trends in allergen immunotherapy, which largely persist today. Shots, despite being the bread and butter of U.S. allergy clinics, are vastly underused. Just 2 or 3 percent of newly diagnosed patients who are recommended for the treatment, actually choose it. Relative to the hordes of patients buying over-the-counter Zyrtec, Thompson said, the number who receive immunotherapy “doesn’t even register.”

One way to make a dent, Thompson figured, was to “offer a therapy people will want.” Thompson opened a second practice, Aspire Allergy & Sinus, in 2012, with a focus on sublingual drops. By then, SLIT seemed promising, Thompson said. “We thought, gosh, this is such a great opportunity.” 

A decade later, a similar ambition is fueling direct-to-consumer companies.

There are trade-offs between in-clinic and at-home allergy testing and treatment. When it comes to allergy diagnoses, physicians typically take a detailed clinical history and then use testing, if needed, to confirm the patient’s allergies. Skin testing is the preferred diagnostic among allergists. It has a quick, visual readout—red lumps, or wheals, that form on the patient’s skin 15 to 30 minutes after getting pricked with potential allergens during an office procedure—but it can’t be done at home.

A second type of test checks a patient’s blood for immune proteins called immunoglobulin E (IgE) antibodies. IgE antibodies bind to a specific allergen—say, pollen or peanut—and trigger release of the chemical histamine, which makes people sneeze, itch, swell up, and, occasionally, go into anaphylaxis. Patients can get the blood test at a lab or, increasingly, at home; some online companies sell kits where customers use a provided finger-prick device to apply drops of their blood onto a card, which they can mail to a lab for analysis.

But blood tests can be tricky to interpret, said Robert G. Hamilton, an expert in diagnostic allergy and immunology testing at Johns Hopkins University School of Medicine. A positive result signals the presence of IgE antibody, which “means you’ve become sensitized to the substance,” he said, “but it doesn’t mean you will manifest any allergic symptoms.”

There’s another potential snag. If a patient purchases a home kit and receives results before talking with a physician, confirmation bias can creep in, said Edwin Kim, an allergist-immunologist at the University of North Carolina School of Medicine. If a patient tests positive for dust, for example, the doctor could “ask a thousand questions on dust” until they think they can prove that the patient is “dust-allergic,” he said.

Still, at-home tests and procedures can reach a far broader pool of patients, as it can be difficult to get an in-person appointment with an allergist. At Oregon Health and Science University, “we are booked out through the end of the year,” said allergist-immunologist Shyam Joshi. And at UNC School of Medicine, an academic hub that draws referrals from all over the state and even neighboring states, Kim sees firsthand how patients struggle with their treatment schedule. “We may see them as a great candidate for allergy shots, but you can’t realistically ask people to drive two, three, four hours every week, week after week,” he said.

And allergy shots are not risk-free. While the process goes smoothly for many patients, some develop red, swollen arms after their injection. Occasionally, a shot can trigger an asthma flare-up or a whole-body anaphylactic reaction, said Nikhila Schroeder, an allergist in Huntersville, North Carolina, recalling her own observations about a decade ago when administering shots during her allergy and immunology fellowship. Given all these limitations, “I started to just wonder,” Schroeder said, “Are there any other ways we could do this?”

More recently, that same realization hit Gene Kakaulin, a New York City health care entrepreneur. He was commiserating with a friend in 2018 about his allergies to cats, dust, and pollens, and how things had gotten so bad in his teen years that he tried shots. They were “a pain,” said Kakaulin. “I couldn’t stick with them.” 

By contrast, home therapy has lower time demands and less pain and risk—while still desensitizing the immune system by repeated exposures to the allergen. Both approaches produce similar immune changes, though their speed and magnitude, and the types of antibodies involved, can differ. Generally, the immune effects show up faster and stronger with shots, whereas they might take longer with sublingual treatment. It’s hard to compare these changes scientifically—especially since immunotherapy is usually a personalized treatment with dose amounts and escalations tailored to each patient, said Schroeder, whose North Carolina allergy clinic specializes in SLIT.

In studies that have tried to compare the immunotherapy approaches head-to-head, shots seem to do “the same or better” on effectiveness, said Hugh Windom, an allergist in Sarasota, Florida, and on safety, “SLIT always wins.”

Sublingual immunotherapy has been available in the U.S. for decades. SLIT drops, which can treat many different allergens together and are not covered by the Food and Drug Administration, have been offered by at least one allergy clinic since 1970, and by pioneering ENT physicians since the 2010s. In 2014, the FDA approved several tablets that dissolve under the tongue. Three tablets treat grass or ragweed allergies, and a fourth gained approval in 2017 for dust mite allergies.

Still, only about 15 percent of some 2 million allergy immunotherapy patients in the U.S. are using a sublingual version, with the majority on drops, according to market research provided to Undark by Jorge Alderete, who has advised direct-to-consumer allergy companies and other health care startups, and serves on the board of a private equity-backed allergy practice in Houston. An estimated 85 percent of U.S. allergy immunotherapy patients are receiving shots.

One reason is tradition. “We are, of course, wedded to shots because we’ve been doing them for a hundred years,” said Windom.

Another reason relates to versatility. Most allergy patients are allergic to more than one substance, yet allergists tend to prefer FDA-approved products—SLIT tablets—and they only treat a single allergen. Shots, on the other hand, can be tailored to treat many of the patient’s allergens at once. In use for more than a century, allergy shots came to be regulated by the FDA and typically get covered by insurance. SLIT drops can also be customized for multiple allergies, but since the extracts are not FDA-approved for under-the-tongue use and do not have a billing code, patients often must pay out of pocket.

Clinic revenue also plays a role. When an allergist sees a patient and recommends a medication, such as an antihistamine, they charge for a single office visit. Allergy shots bring in more revenue. (Exactly how much revenue can be difficult to estimate, as costs can vary significantly clinic to clinic.) When a patient goes on the shots, three to five years of office treatments at weekly to monthly intervals can amount to dozens of billable visits. Plus, with each visit the clinic charges for mixing the specialized treatment and administering the shot, said Alderete. From a business perspective, he said, immunotherapy is “an annuity.” 

Unlike shots, which are billed as a procedure, SLIT tablets are a prescribed drug. “If you’re going to ask an allergist, hey, do you want to do shots and make money off of it, or prescribe something to Walgreens,” Kim said, it’s understandable that tablets aren’t preferred by allergists in the U.S. Customized SLIT drops are prepared in-house at some clinics, or physicians can send the prescription to a compounding pharmacy.

In the drops form, SLIT does square well with shots on versatility—both can address combinations of allergens with adjustable dosing and escalations—but per-patient profit margins can be higher with shots, said Alderete.

This is in part because of doctors’ costs associated with purchasing and preparing the allergen extracts. Though different forms of immunotherapies use the same source material, SLIT preparations can be “significantly more concentrated than even the top doses of allergy shots,” said allergist and immunologist Sakina Bajowala, who offers both treatments at her allergy practice outside of Chicago. In one analysis of immunotherapy regimens for birch allergy, the total amount of allergen administered over the course of a year was 30 times greater with SLIT compared with shots. And office-made SLIT, Bajowala said, can make doctors’ margins even slimmer: “The more extract used, the more costly the drops.”

ENT practices are more willing to offer a less lucrative therapy because, unlike allergists, their revenue mostly comes from surgeries, so SLIT is “a bit of an ancillary service,” said Thompson.

But on the whole, SLIT drops remain far from mainstream, even as interest in this mode of treatment grows.

After hearing about his friend’s needle-free therapy—SLIT drops—Kakaulin made a round of calls to practices in New York so he could try SLIT himself. His symptoms improved “within a few months,” which helped him sleep and exercise better, he said. To this day, the drops remain a part of Kakaulin’s morning routine—“two minutes under the tongue right after brushing teeth when I shave.” 

Along the way, he co-founded Curex, one of several online allergy companies that got off the ground during the pandemic as telemedicine soared. While just 1 percent of allergy appointments took place virtually before the pandemic, that figure jumped to 54 percent one month into lockdown. Across medicine, telehealth shot up 78-fold between February 2020 and April 2020, according to an analysis, from the consulting firm McKinsey, and after a year remained 38 times higher than pre-pandemic.

Meanwhile, brick-and-mortar clinics took a hit. “A lot of allergy offices closed because of Covid concerns, and then people who were supposed to get shots were left out in the cold,” said Kim.

Direct-to-consumer allergy companies capitalized on this perfect storm, luring customers with glowing testimonials, free quizzes, and heaps of online advertising. Their social media ads showcase sublingual drops as a “convenient alternative to allergy shots” with “no trips to the doctor’s office or prickly needles.”

Some of these companies also offer allergy testing. Curex can send a phlebotomist to administer blood tests to patients with eligible zip codes. Wyndly, a company headquartered in Lakewood, Colorado, ships a $249 test kit to the customer’s home. New York City-based Nectar also sells home tests and lets patients upload results of previous allergy testing. Based on test results and a medical consult, the companies sell formulated sublingual drops on subscription plans, some at $99 per month or less. “We think there are tens of millions of Americans who could benefit,” said Kakaulin, who had helped start a prescription savings company before launching Curex in 2020.

To reach those millions of potential customers, companies that sell allergy drops face similar financial challenges as allergy practices. The average SLIT patient “produces 70 or 80 percent less revenue than an allergy shot patient,” Kakaulin said. So instead of trying to maximize per-patient profit, Curex is trying to “maximize some of our efficiencies and provide everyday low prices,” he said.

Toward this end, nationwide direct-to-consumer companies, as well as large multi-site allergy practices, can negotiate lower pricing on allergen extracts and other supplies because they order huge volumes. Small practices often do not get these discounts and thus have higher backend costs if they choose to offer off-label SLIT.

Amid these financial considerations, there’s also a mindset difference between serving patients and winning customers. With a business model that relies on “one thing,” Bajowala said, it’s in a direct-to-consumer company’s interest to create ads that say, “well, the thing we’re offering is the best, so why would you even want to consider the other thing?”

Some allergists worry that direct-to-consumer companies hasten a broader trend: the decline of the practitioner-patient relationship. When patients begin a new treatment, they “need to know when is it going to start working, how to monitor for side effects, and if there’s a problem, who are you going to go to?” said Anne Maitland, an allergist-immunologist at Icahn School of Medicine at Mount Sinai in New York City and the director of allergy and immunology at the Metrodora Institute in Salt Lake City, Utah. 

At direct-to-consumer companies, details about what’s in the treatment and who’s providing the medical care are also somewhat of a black box. Pressey, the Merchant Marine with the cat allergy, said that if he were to request a consult at Curex, for instance, it would not be with the provider who did his intake. “That person doesn’t work there anymore,” he said. And if he ever wanted to stop his subscription and continue SLIT treatment elsewhere, Curex does not “give you the exact mixture that you’re getting treated for,” Pressey said.

As for staffing, Nectar relies heavily on primary care physicians with training in allergy immunotherapy, but a public relations spokesperson denied a request to interview one of these providers. Regarding the number of doctors in the Curex network, Kakaulin declined to answer. “I’d rather not talk about specifics of the business,” he said. “We’d prefer to have certain information kind of private.”

While the approach lacks transparency, patients often can’t access information in traditional health care settings, either. In a health care system that favors standardized protocols, insurance reimbursements and clinic business priorities may compel physicians to recommend certain treatments, making it hard for patients to learn about the full spectrum of options, said Schroeder, whose clinic offers SLIT using a direct-care model, where patients pay the provider directly rather than using traditional fee-for-service insurance. 

In fact, the allergy clinic might be one of the hardest places to get clear information about treatment options. That’s in part because of a lawsuit from almost a decade ago. In 2014, the American Academy of Allergy, Asthma & Immunology (AAAAI), American College of Allergy, Asthma & Immunology (ACAAI), and several other allergy groups were sued by United Allergy Services, a company that helps primary care physicians and other non-specialists diagnose and treat allergies.

The company alleged that allergists who decried UAS practices were restricting the market and limiting patient access to allergen immunotherapy. As part of a settlement, the allergy groups issued a policy statement requiring members to minimize litigation risk by complying with antitrust laws. As Matt Bell, an allergist in Fayetteville, Arkansas, explained it, the lawsuit is “why we are hesitant to talk.” The settlement terms “basically stated that AAAAI had to keep their mouths shut,” said David Stukus, an allergist at Nationwide Children’s Hospital in Columbus, Ohio, who declined to speak about specific companies or services.

And depending on where and how a patient finds SLIT, their experiences can vary widely. With rising demand for allergy care and limited allergist availability, patients can get allergy treatment from many sources besides their local allergist — including ENT practices, primary care doctors, pediatricians, urgent care, emergency rooms, naturopathic doctors, and direct-to-consumer companies. “If you do SLIT at different places, it won’t necessarily be the same. The people may have different levels of expertise,” said Schroeder, who learned the ins and outs of sublingual therapy at Allergy Associates of La Crosse, a Wisconsin clinic that has offered this treatment for environmental and food allergies since 1970. Nevertheless, she said, there’s a role for all these various avenues as long as patients understand the complexities and “know what they’re pursuing.”

So far, the direct-to-consumer drops seem to be working well for Pressey. Before starting treatment in 2021, he struggled with frequent allergy-induced asthma attacks. “I couldn’t make it 24 hours with a cat in the house,” he said in a latest interview. Now “it’s about two and half weeks before I even remember that I have asthma.” 

Pressey still has questions about the therapy and about Curex—like how long the benefits will last and whether the company will survive. Even when scouring Reddit in spring 2021, he could not find answers to these questions. Nevertheless, “I’m a firm believer in new technology,” he said. “You know what, if no one tries it, then no one will ever get the answers.”

This article was originally published on Undark. Read the original article.

A new health care apprenticeship program at AdventHealth is helping young adults in our area build strong careers in the medical field. These students, carefully selected from their respective communities, are gaining valuable skills and experience in phlebotomy, which is taking and preparing patient blood samples for testing.

AdventHealth and Ultimate Medical Academy were chosen to partner with CareerSource Tampa Bay and the Hillsborough Board of County Commissioners to implement the first health care Apprenticeship-to-Career Empowerment Program (ACE). CareerSource Tampa Bay and the Hillsborough Board of County Commissioners have already worked together for three years on providing paths for other career fields, but this is the first of their programs in health care.

The program includes the opportunity for them to earn a professional career certificate, gain paid work experience, and have assistance in preparation for entering the professional workforce. It also starts them on the path to becoming a nationally certified laboratory assistant.

“The Phlebotomy program focuses specifically on phlebotomy as a part of Laboratory Assisting. These students will earn a career certificate from the National Healthcareer Association and are also learning to assist Medical Laboratory Scientists in our AdventHealth hospital laboratories,” said Mistie Palmer, AdventHealth Learning Operations Manager.“AdventHealth recognizes that these team members are crucial to the Medical Laboratory Team in providing expert, whole-person care to our community.” 

Employment of phlebotomists is projected to grow 10 percent from 2021 to 2031, faster than the average for all occupations, according to the U.S. Bureau of Labor Statistics. Florida also has one of the highest employment levels for phlebotomists in the country.

This partnership between AdventHealth and UMA, combined with the support of CareerSource, has created an environment where aspiring individuals can find their footing and embark on a journey in the medical field.

This current group of students will have the chance to apply for AdventHealth positions.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world, associated with symptoms like memory loss and cognitive impairment. Brain lesions caused by the aggregation of amyloid β (Aβ) and neurofibrillary tangles are believed to be the main cause of AD. Therefore, therapeutic agents that control Aβ aggregation may be useful in delaying the onset and progression of AD.

While many drugs targeting Aβ have been developed, they have failed to demonstrate efficacy in clinical trial studies. Moreover, the use of approved antibody drugs is associated with high costs of treatment and uncertain efficacy. Therefore, developing a simple and efficient drug that targets Aβ for the treatment of AD is needed.

One such therapeutic agent could be phyllodulcin, a natural sweetening agent found in Hydrangea macrophylla var. thunbergia. Previous studies have shown that phyllodulcin, a type of polyphenol, can efficiently penetrate the blood-brain barrier and get uniformly distributed in the brain. Moreover, latest research also suggests that polyphenols can inhibit Aβ aggregation. However, the role of phyllodulcin for the management of AD has not been studied.

To fill this knowledge gap, Assistant Professor Se Jin Jeon of the Department of Integrative Biotechnology, College of Science and Technology, Sahmyook University, along with a group of researchers from Korea, studied the effect of phyllodulcin on Aβ aggregation and various pathological features in an animal model of AD.

Their study was published in Biomedicine & Pharmacotherapy.

Speaking about the rationale behind this study, Assistant Professor Jeon says, "We focused on increasing the level of evidence regarding phyllodulcin by using various experimental techniques. We hypothesized that phyllodulcin may enter the brain and inhibit Aβ aggregation, resulting in the improvement of various brain lesions appearing in AD. To examine our hypothesis, we investigated the effect of phyllodulcin on the Aβ aggregation and various pathological hallmarks in an animal model of AD."

The researchers demonstrated that phyllodulcin could efficiently inhibit Aβ aggregation as well as decompose pre-aggregated Aβ clumps, both in in vivo (cells) and in vitro (animal model) experiments. Moreover, a toxicity assay revealed that phyllodulcin prevents Aβ-induced neurotoxicity and attributed this to the reduced Aβ aggregates.

For the in vivo experiments, the researchers used male 5XFAD mice (a strain of transgenic mice) for creating AD model and wild-type mice. They were orally administered with either phyllodulcin or a control drug, once every three days for a month. The mice were then subjected to electrophysiological and immunohistochemical analyses. The results revealed that phyllodulcin reduced the memory impairments caused by the accumulation of amyloid proteins.

The hippocampus is the site for memory formation, which is inhibited by Aβ clumps in AD, leading to memory loss. Interestingly, the experiments revealed that phyllodulcin could counter this effect by reducing the deposition of Aβ in the hippocampus and increasing memory-related processes. Additionally, it also minimized neuroinflammation in the hippocampus and inhibited the activation of microglia and astrocytes (cells responsible for playing a key role in neuroinflammation in the pathology of AD).

Elaborating further on these findings, Assistant Professor Jeon says, "Our study is the first to report that phyllodulcin can modify the underlying pathogenesis of Alzheimer's disease, suggesting the possibility of preventing dementia or delaying the progression of the disease."

"It will take more than 20 years to develop a treatment, but at this stage, the results of this study can be used to provide a guide map that can help prevent or Improve dementia symptoms."

Provided by Sahmyook University

For as long as he can remember, Ken Pressey has had severe allergies to cats. They would trigger hives, runny nose, and watery eyes. Still, like many of the tens of millions of people in the United States who suffer from allergies, Pressey for years did not bother getting treated, or even diagnosed. When cats came near, he just avoided them.

But that tactic has gotten tougher. During the pandemic, Pressey started dating a woman he's now engaged to marry — and she has two cats. Being with the cats "was absolute chaos," said the 30-year-old, who lives in Seattle. "I started having asthma attacks."

Pressey's primary care physician suggested allergy shots. This century-old approach, a form of immunotherapy, works by exposing the body to small, increasing doses of the culprit substance. Unlike over-the-counter pills and nasal sprays, which only relieve symptoms, shots address the root cause: They help the body build long-term tolerance to the allergens. The treatment is not a cure, but experts say it can bring relief in around 85 percent of patients who try it. And it's not just a matter of curbing some sneezing. Beyond springtime sniffles, allergies make it hard to concentrate, leading to missed work and school. They can also disrupt sleep, trigger asthma, and contribute to mood disorders.

The procedure for alleviating this misery with allergy shots requires time and diligence. Typically, patients need injections once or twice a week for the first three to six months, then monthly jabs for three to five years. Each office visit also requires a half hour of monitoring after the shot in case of serious reactions, such as wheezing or throat swelling, which are rare but need immediate attention if they occur.

With these scheduling demands, allergy shots were a no-go for Pressey, an engineer with the United States Merchant Marines who often works overseas for months at a time. "I would not be able to keep up," he said. While looking into alternatives, he recalled a conversation about allergy treatments while stationed in Europe several years earlier, when he heard a coworker say, "We do allergy drops. We don't do shots. Why would you want to get stabbed by a needle?"

His colleague was referring to a form of sublingual immunotherapy, or SLIT, which builds immune tolerance to allergens administered daily under the tongue. The drops are formulated using the same liquid extracts in skin-based allergy tests, and research suggests the approach works — and is safe for patients to do at home. SLIT drops are a mainstay in Europe, Canada, and Latin America. In the United States, although some medical providers offer the drops off-label, prescribing the treatment remains limited for complex reasons related to regulatory purview and clinic revenue.

That means accessing SLIT drops can be tricky, even for highly motivated patients. "I did quite a bit of extensive reading," Pressey said. The hardest part, he added, was finding a SLIT provider. Although he managed to connect with several doctors who offer the drops, their clinics were far away. Eventually Pressey went to a forum for allergies on Reddit, which led him to try a consult with Curex, one of more than a half dozen virtual health companies that have started selling allergy tests and SLIT directly to consumers.

Some of these companies launched during the pandemic when telehealth was rising and Covid concerns kept some allergy sufferers from going to clinic to get shots. The companies' services focus on diagnosis and treatment of environmental allergies such as pets, dust, pollens, and grasses.

As more health services move online, patients have greater access to treatments but often sacrifice the continuity of traditional physician-patient relationships. As with other areas of medicine, finding allergy care has become a buyer-beware dilemma: Financial incentives and legal complications prevent SLIT from going mainstream with allergists, and so the challenge of making this treatment available and cost-effective has largely landed in the hands of non-allergist practitioners and business executives.

Allergen immunotherapy traces its roots to a pioneering experiment published in 1911. In that study, a pair of young British researchers rounded up patients and showed that injecting their arms with grass pollen toxins could calm their hay fever — which the researchers measured by dripping pollen extract into the patients' eyes and noting the extent of burning and itching. With little understanding of the cells and molecules involved, physicians refined this method and, in 1954, confirmed its benefits in a double-blind trial. 

As the shots regimen gained popularity with physicians, the procedure proved quite safe overall, but news of several patient deaths in the early 1980s led some researchers to explore other ways to treat allergies without injections. Their efforts gave rise to sublingual immunotherapy — the liquid drops now offered by direct-to-consumer companies — and, initially, otolaryngologists, or ear, nose, and throat specialists saw potential in what appeared to be a gentler, more convenient allergy treatment.

Otolaryngology is primarily a surgical specialty. But allergies lie at the root of some of the complications that ENT physicians treat, and often present a roadblock. Whenever allergies cropped up as an underlying cause for his patients' polyps and nasal disease, they "would never go for allergy therapy because, you know, it was always just shots," said Chris Thompson, an ENT-trained head and neck surgeon in Austin, Texas, who opened his practice in 1997.

Over the next decade, research continued on sublingual immunotherapy. By 2007, there was "growing consensus that specific sublingual immunotherapy (SLIT) does actually work," according to one review in the Journal of Allergy and Clinical Immunology. In a 2009 position paper, the World Allergy Organization acknowledged SLIT as a viable treatment. Enterprising doctors began offering this type of immunotherapy.

Still, key details about the technique, such as what doses are needed to achieve benefit, seemed murky. "You could literally go to one doctor and get something that was 10,000 times weaker than what you might get from another doctor," Thompson said. "There was no standardization." 

Allergists were intrigued by sublingual therapy, but very few at the time offered it in clinic. According to a 2007 survey by the American College of Allergy, Asthma, and Immunology, just 5.9 percent of practicing allergists said they were using SLIT, and by 2011 that figure had only edged up to 11.4 percent. Most respondents cited the lack of FDA-approved products as a barrier.

Nevertheless, interest in sublingual immunotherapy grew in the ENT realm. Professional societies included symposiums about SLIT at their annual meetings and formed subgroups devoted to this new approach. Some otolaryngology group meetings offer courses for physicians to get started with SLIT, Thompson said.

Thompson watched the field a while, noting SLIT's research progress amid overall trends in allergen immunotherapy, which largely persist today. Shots, despite being the bread and butter of U.S. allergy clinics, are vastly underused. Just 2 or 3 percent of newly diagnosed patients who are recommended for the treatment, actually choose it. Relative to the hordes of patients buying over-the-counter Zyrtec, Thompson said, the number who receive immunotherapy "doesn't even register."

One way to make a dent, Thompson figured, was to "offer a therapy people will want." Thompson opened a second practice, Aspire Allergy & Sinus, in 2012, with a focus on sublingual drops. By then, SLIT seemed promising, Thompson said. "We thought, gosh, this is such a great opportunity." 

A decade later, a similar ambition is fueling direct-to-consumer companies.

There are trade-offs between in-clinic and at-home allergy testing and treatment. When it comes to allergy diagnoses, physicians typically take a detailed clinical history and then use testing, if needed, to confirm the patient's allergies. Skin testing is the preferred diagnostic among allergists. It has a quick, visual readout — red lumps, or wheals, that form on the patient's skin 15 to 30 minutes after getting pricked with potential allergens during an office procedure — but it can't be done at home.

A second type of test checks a patient's blood for immune proteins called immunoglobulin E (IgE) antibodies. IgE antibodies bind to a specific allergen — say, pollen or peanut — and trigger release of the chemical histamine, which makes people sneeze, itch, swell up, and, occasionally, go into anaphylaxis. Patients can get the blood test at a lab or, increasingly, at home; some online companies sell kits where customers use a provided finger-prick device to apply drops of their blood onto a card, which they can mail to a lab for analysis.

But blood tests can be tricky to interpret, said Robert G. Hamilton, an expert in diagnostic allergy and immunology testing at Johns Hopkins University School of Medicine. A positive result signals the presence of IgE antibody, which "means you've become sensitized to the substance," he said, "but it doesn't mean you will manifest any allergic symptoms."

There's another potential snag. If a patient purchases a home kit and receives results before talking with a physician, confirmation bias can creep in, said Edwin Kim, an allergist-immunologist at the University of North Carolina School of Medicine. If a patient tests positive for dust, for example, the doctor could "ask a thousand questions on dust" until they think they can prove that the patient is "dust-allergic," he said.

Still, at-home tests and procedures can reach a far broader pool of patients, as it can be difficult to get an in-person appointment with an allergist. At Oregon Health and Science University, "we are booked out through the end of the year," said allergist-immunologist Shyam Joshi. And at UNC School of Medicine, an academic hub that draws referrals from all over the state and even neighboring states, Kim sees firsthand how patients struggle with their treatment schedule. "We may see them as a great candidate for allergy shots, but you can't realistically ask people to drive two, three, four hours every week, week after week," he said.

And allergy shots are not risk-free. While the process goes smoothly for many patients, some develop red, swollen arms after their injection. Occasionally, a shot can trigger an asthma flare-up or a whole-body anaphylactic reaction, said Nikhila Schroeder, an allergist in Huntersville, North Carolina, recalling her own observations about a decade ago when administering shots during her allergy and immunology fellowship. Given all these limitations, "I started to just wonder," Schroeder said, "Are there any other ways we could do this?"

More recently, that same realization hit Gene Kakaulin, a New York City health care entrepreneur. He was commiserating with a friend in 2018 about his allergies to cats, dust, and pollens, and how things had gotten so bad in his teen years that he tried shots. They were "a pain," said Kakaulin. "I couldn't stick with them." 

By contrast, home therapy has lower time demands and less pain and risk — while still desensitizing the immune system by repeated exposures to the allergen. Both approaches produce similar immune changes, though their speed and magnitude, and the types of antibodies involved, can differ. Generally, the immune effects show up faster and stronger with shots, whereas they might take longer with sublingual treatment. It's hard to compare these changes scientifically — especially since immunotherapy is usually a personalized treatment with dose amounts and escalations tailored to each patient, said Schroeder, whose North Carolina allergy clinic specializes in SLIT.

In studies that have tried to compare the immunotherapy approaches head-to-head, shots seem to do "the same or better" on effectiveness, said Hugh Windom, an allergist in Sarasota, Florida, and on safety, "SLIT always wins."

Sublingual immunotherapy has been available in the U.S. for decades. SLIT drops, which can treat many different allergens together and are not covered by the Food and Drug Administration, have been offered by at least one allergy clinic since 1970, and by pioneering ENT physicians since the 2010s. In 2014, the FDA approved several tablets that dissolve under the tongue. Three tablets treat grass or ragweed allergies, and a fourth gained approval in 2017 for dust mite allergies.

Still, only about 15 percent of some 2 million allergy immunotherapy patients in the U.S. are using a sublingual version, with the majority on drops, according to market research provided to Undark by Jorge Alderete, who has advised direct-to-consumer allergy companies and other health care startups, and serves on the board of a private equity-backed allergy practice in Houston. An estimated 85 percent of U.S. allergy immunotherapy patients are receiving shots.

One reason is tradition. "We are, of course, wedded to shots because we've been doing them for a hundred years," said Windom.

Another reason relates to versatility. Most allergy patients are allergic to more than one substance, yet allergists tend to prefer FDA-approved products — SLIT tablets — and they only treat a single allergen. Shots, on the other hand, can be tailored to treat many of the patient's allergens at once. In use for more than a century, allergy shots came to be regulated by the FDA and typically get covered by insurance. SLIT drops can also be customized for multiple allergies, but since the extracts are not FDA-approved for under-the-tongue use and do not have a billing code, patients often must pay out of pocket.

Clinic revenue also plays a role. When an allergist sees a patient and recommends a medication, such as an antihistamine, they charge for a single office visit. Allergy shots bring in more revenue. (Exactly how much revenue can be difficult to estimate, as costs can vary significantly clinic to clinic.) When a patient goes on the shots, three to five years of office treatments at weekly to monthly intervals can amount to dozens of billable visits. Plus, with each visit the clinic charges for mixing the specialized treatment and administering the shot, said Alderete. From a business perspective, he said, immunotherapy is "an annuity." 

Unlike shots, which are billed as a procedure, SLIT tablets are a prescribed drug. "If you're going to ask an allergist, hey, do you want to do shots and make money off of it, or prescribe something to Walgreens," Kim said, it's understandable that tablets aren't preferred by allergists in the U.S. Customized SLIT drops are prepared in-house at some clinics, or physicians can send the prescription to a compounding pharmacy.

In the drops form, SLIT does square well with shots on versatility — both can address combinations of allergens with adjustable dosing and escalations — but per-patient profit margins can be higher with shots, said Alderete.

This is in part because of doctors' costs associated with purchasing and preparing the allergen extracts. Though different forms of immunotherapies use the same source material, SLIT preparations can be "significantly more concentrated than even the top doses of allergy shots," said allergist and immunologist Sakina Bajowala, who offers both treatments at her allergy practice outside of Chicago. In one analysis of immunotherapy regimens for birch allergy, the total amount of allergen administered over the course of a year was 30 times greater with SLIT compared with shots. And office-made SLIT, Bajowala said, can make doctors' margins even slimmer: "The more extract used, the more costly the drops."

ENT practices are more willing to offer a less lucrative therapy because, unlike allergists, their revenue mostly comes from surgeries, so SLIT is "a bit of an ancillary service," said Thompson.

But on the whole, SLIT drops remain far from mainstream, even as interest in this mode of treatment grows.

After hearing about his friend's needle-free therapy — SLIT drops — Kakaulin made a round of calls to practices in New York so he could try SLIT himself. His symptoms improved "within a few months," which helped him sleep and exercise better, he said. To this day, the drops remain a part of Kakaulin's morning routine — "two minutes under the tongue right after brushing teeth when I shave." 

Along the way, he co-founded Curex, one of several online allergy companies that got off the ground during the pandemic as telemedicine soared. While just 1 percent of allergy appointments took place virtually before the pandemic, that figure jumped to 54 percent one month into lockdown. Across medicine, telehealth shot up 78-fold between February 2020 and April 2020, according to an analysis, from the consulting firm McKinsey, and after a year remained 38 times higher than pre-pandemic.

Meanwhile, brick-and-mortar clinics took a hit. "A lot of allergy offices closed because of Covid concerns, and then people who were supposed to get shots were left out in the cold," said Kim.

Direct-to-consumer allergy companies capitalized on this perfect storm, luring customers with glowing testimonials, free quizzes, and heaps of online advertising. Their social media ads showcase sublingual drops as a "convenient alternative to allergy shots" with "no trips to the doctor's office or prickly needles."

Some of these companies also offer allergy testing. Curex can send a phlebotomist to administer blood tests to patients with eligible zip codes. Wyndly, a company headquartered in Lakewood, Colorado, ships a $249 test kit to the customer's home. New York City-based Nectar also sells home tests and lets patients upload results of previous allergy testing. Based on test results and a medical consult, the companies sell formulated sublingual drops on subscription plans, some at $99 per month or less. "We think there are tens of millions of Americans who could benefit," said Kakaulin, who had helped start a prescription savings company before launching Curex in 2020.

To reach those millions of potential customers, companies that sell allergy drops face similar financial challenges as allergy practices. The average SLIT patient "produces 70 or 80 percent less revenue than an allergy shot patient," Kakaulin said. So instead of trying to maximize per-patient profit, Curex is trying to "maximize some of our efficiencies and provide everyday low prices," he said.

Toward this end, nationwide direct-to-consumer companies, as well as large multi-site allergy practices, can negotiate lower pricing on allergen extracts and other supplies because they order huge volumes. Small practices often do not get these discounts and thus have higher backend costs if they choose to offer off-label SLIT.

Amid these financial considerations, there's also a mindset difference between serving patients and winning customers. With a business model that relies on "one thing," Bajowala said, it's in a direct-to-consumer company's interest to create ads that say, "well, the thing we're offering is the best, so why would you even want to consider the other thing?"

Some allergists worry that direct-to-consumer companies hasten a broader trend: the decline of the practitioner-patient relationship. When patients begin a new treatment, they "need to know when is it going to start working, how to monitor for side effects, and if there's a problem, who are you going to go to?" said Anne Maitland, an allergist-immunologist at Icahn School of Medicine at Mount Sinai in New York City and the director of allergy and immunology at the Metrodora Institute in Salt Lake City, Utah.

At direct-to-consumer companies, details about what's in the treatment and who's providing the medical care are also somewhat of a black box. Pressey, the Merchant Marine with the cat allergy, said that if he were to request a consult at Curex, for instance, it would not be with the provider who did his intake. "That person doesn't work there anymore," he said. And if he ever wanted to stop his subscription and continue SLIT treatment elsewhere, Curex does not "give you the exact mixture that you're getting treated for," Pressey said.

As for staffing, Nectar relies heavily on primary care physicians with training in allergy immunotherapy, but a public relations spokesperson denied a request to interview one of these providers. Regarding the number of doctors in the Curex network, Kakaulin declined to answer. "I'd rather not talk about specifics of the business," he said. "We'd prefer to have certain information kind of private."

While the approach lacks transparency, patients often can't access information in traditional health care settings, either. In a health care system that favors standardized protocols, insurance reimbursements and clinic business priorities may compel physicians to recommend certain treatments, making it hard for patients to learn about the full spectrum of options, said Schroeder, whose clinic offers SLIT using a direct-care model, where patients pay the provider directly rather than using traditional fee-for-service insurance. 

In fact, the allergy clinic might be one of the hardest places to get clear information about treatment options. That's in part because of a lawsuit from almost a decade ago. In 2014, the American Academy of Allergy, Asthma & Immunology (AAAAI), American College of Allergy, Asthma & Immunology (ACAAI), and several other allergy groups were sued by United Allergy Services, a company that helps primary care physicians and other non-specialists diagnose and treat allergies.

The company alleged that allergists who decried UAS practices were restricting the market and limiting patient access to allergen immunotherapy. As part of a settlement, the allergy groups issued a policy statement requiring members to minimize litigation risk by complying with antitrust laws. As Matt Bell, an allergist in Fayetteville, Arkansas, explained it, the lawsuit is "why we are hesitant to talk." The settlement terms "basically stated that AAAAI had to keep their mouths shut," said David Stukus, an allergist at Nationwide Children's Hospital in Columbus, Ohio, who declined to speak about specific companies or services.

And depending on where and how a patient finds SLIT, their experiences can vary widely. With rising demand for allergy care and limited allergist availability, patients can get allergy treatment from many sources besides their local allergist — including ENT practices, primary care doctors, pediatricians, urgent care, emergency rooms, naturopathic doctors, and direct-to-consumer companies. "If you do SLIT at different places, it won't necessarily be the same. The people may have different levels of expertise," said Schroeder, who learned the ins and outs of sublingual therapy at Allergy Associates of La Crosse, a Wisconsin clinic that has offered this treatment for environmental and food allergies since 1970. Nevertheless, she said, there's a role for all these various avenues as long as patients understand the complexities and "know what they're pursuing."

So far, the direct-to-consumer drops seem to be working well for Pressey. Before starting treatment in 2021, he struggled with frequent allergy-induced asthma attacks. "I couldn't make it 24 hours with a cat in the house," he said in a latest interview. Now "it's about two and half weeks before I even remember that I have asthma." 

Pressey still has questions about the therapy and about Curex — like how long the benefits will last and whether the company will survive. Even when scouring Reddit in spring 2021, he could not find answers to these questions. Nevertheless, "I'm a firm believer in new technology," he said. "You know what, if no one tries it, then no one will ever get the answers."

This article was originally published on Undark. Read the original article.

An experimental malaria vaccine appears safe and promotes an immune response in African infants, one of the groups most vulnerable to severe malaria disease.

There is currently only one malaria vaccine, "RTS,S" that is approved by the World Health Organization and offers partial disease protection. However, in the results of the early-stage phase Ib trial conducted in Tanzania and published on August 11th in the journal Med, researchers find that targeting RH5—a protein that the malaria pathogen Plasmodium falciparum uses to invade red blood cells—can generate a promising immune response that is most pronounced in an infant cohort.

"Anti-sporozoite vaccines such as RTS,S need to be 100% effective in stopping the parasite from invading the liver to prevent disease," says senior author Angela Minassian, a clinician scientist at the University of Oxford.

"Even if just one parasite slips through the net, this will then go on to multiply in the liver, burst out into the bloodstream, and then infect red blood cells where the parasites then grow at an exponential rate. Having a blood-stage vaccine like RH5 on board gives you a second line of defense once the parasite has entered the bloodstream, allowing a second chance to stop malaria before it causes illness."

A person is infected with malaria when bitten by an infected mosquito, which releases Plasmodium falciparum into the body. RTS,S and many other vaccine candidates teach the immune system how to target the parasite at this sporozoite stage, before it invades the liver.

Once the parasite matures and is released from the liver into the bloodstream, Plasmodium falciparum displays RH5 and infects red blood cells, which causes disease. If an anti-sporozoite and an anti-RH5 vaccine were used in combination in the future, individuals could potentially experience more effective protection against malaria for a longer period of time.

"The data in the phase 1b trial reported here confirm, for the first time, that substantial anti-RH5 immune responses can be achieved safely by vaccination in infants from a malaria-endemic area," say the authors.

The researchers conducted the vaccine trial in Bagamoyo, Tanzania, where the average malaria prevalence throughout the population is 13%. 63 participants aged six months to 35 years were enrolled and randomized to receive either the experimental malaria vaccine, called "ChAd63-MVA RH5," or a control rabies vaccine. The trial was also double-blinded, meaning that neither the participants nor the vaccine administrators knew who received the malaria vaccine or the control.

All participants were given the second dose of vaccine two months later and followed for four months after this.

The primary purpose of this study was to evaluate the safety of this vaccine in a population where malaria is endemic. Participants in both the control and treatment group reported pain at the injection site and a mild fever shortly after vaccination, but overall the vaccine was well tolerated and there were no safety concerns.

A secondary outcome of the study was whether the vaccine would promote an immune response. Researchers found that participants who received the malaria vaccine developed antibodies against RH5 in their blood upon follow-up. In the laboratory, these antibodies were able to inhibit the growth of the malaria parasite at high levels that are associated with disease protection.

"These data justify onward progression to phase IIb field efficacy trials to determine whether parasite growth-inhibition levels of this magnitude can ultimately protect against clinical malaria," say the authors.

The authors note that they observed the strongest immune responses in infants under 11 months, followed by children aged one to six years, then adults. "Why the infants and young children vaccinated with ChAd63-MVA RH5 induced such high levels of antibody remains to be fully understood," say the authors. "Given that both anti-sporozoite and blood-stage malaria vaccine strategies necessitate very high levels of antibody to protect against parasite infection, current efforts remain focused on infants and young children."

The researchers note that this was a small study that followed participants for only four months after receiving their full vaccine schedule.

They recommend that additional phase Ia/Ib trials should be conducted to optimize the recommended age range, boosting schedule, and delivery platform for anti-RH5 vaccines. Currently, a phase 1b trial is planned in the Gambia which will look at the effects of combining an anti-RH5 vaccine with an anti-sporozoite vaccine.

Two of the candidates running for seat 4 on the Medical Lake School Board differ on whether schools should support students who seek gender-affirming care and what books should be allowed in school libraries.

Incumbent Ron Cooper is running for his fifth consecutive term on the city’s school board. Cooper was appointed to the position in 2006 before he was elected for his first full term in seat 4. He said he is running to keep the seat to advocate for students in the schools – including his grandchildren – and to supply back to the community.

“Being the longest person that’s serving right now on our board, I’ve had the opportunity to serve with a lot of really neat people that have kind of mentored me, shown me how things are running.”

Cooper, a longtime sports scoreboard operator with the district, said he is proud of his work on the board to maintain a strong fund balance through hurdles such as the recession and a global pandemic. He also pointed to strong graduation rates – upwards of 90% over the last 10 years, he reported.

Political newcomer Nick Hawkins said he put his hat in the ring because he is a strong supporter of public schools and concerns with his children’s education.

“There’s a way in which we have to address pluralism in our society,” Hawkins said. “We’re not there. We’ve swung totally on the other side and we’re actually discriminating against the vast majority of Orthodox Jews, Orthodox Muslims, Orthodox Christians. Why do we do that in a school when we really need to focus on getting our next generation trained for the jobs of tomorrow?”

Hawkins, a local pastor, said he does not believe students who identify as trans should be allowed to use bathrooms and locker rooms that correspond with their gender identity. He said if an LGBTQ+ support group is allowed to make an announcement on the school’s intercom system each week, so should a Bible club.

“Perhaps the Bible club needs to take place off campus as well as LGBTQ+ support,” he said, “as well as some of the other groups that just are actually in alignment with actually getting kids through reading, writing, arithmetic, science.”

In contrast, Cooper said he believes the school district is obligated to support students in the LGBTQ+ community.

“I don’t think we really have a choice,” Cooper said. “The state says we have to make some type of accommodation. Some people I know disagree with that. But that’s what we need to do.”

In Washington, gender identity and sexual orientation are protected under the state’s nondiscrimination law.

Under state law, students in public schools have the right to use restrooms and locker rooms that correspond with their gender identity, according to the state Office of Superintendent of Public Instruction.

Cooper and Hawkins also disagreed on what books are appropriate for school libraries.

Hawkins said the school library is not the place for books that “incite belief-system battles,” adding that there is a public library right down the street.

“Why are people calling for bans of books? They see certain books as pornography. They see certain books as grooming. They see certain books as a threat to their faith,” Hawkins said. “So their religious liberties are at stake.”

Cooper said he is “not a big fan of censorship.”

“Medical Lake Public Schools is not a private school,” he said. “We should be able to educate our students.”

Both Cooper and Hawkins agreed that teachers should not carry guns in schools, a Topic other school board candidates have differed on in the school board primaries.

The candidate elected for position 4 will serve a four-year term on the Medical Lake School Board.

For the primary election, Aug. 1 is the deadline to register at the polls.

Primary election day is Aug. 1, and ballots are due in drop boxes at 8 p.m. that day.