Author name: Kris Guyer

what-happens-when-dei-becomes-doa-in-the-aerospace-industry?

What happens when DEI becomes DOA in the aerospace industry?

Space / /

As part of the executive order, US companies with federal contracts and grants must certify that they no longer have any DEI hiring practices. Preferentially hiring some interns from a pool that includes women or minorities is such a practice. Effectively, then, any private aerospace company that receives federal funding, or intends to one day, would likely be barred under the executive order from engaging with these kinds of fellowships in the future.

US companies are scrambling to determine how best to comply with the executive order in many ways, said Emily Calandrelli, an engineer and prominent science communicator. After the order went into effect, some large defense contractor companies, including Lockheed Martin and RTX (formerly Raytheon) went so far as to cancel internal employee resource groups, including everything from group chats to meetings among women at the company that served to foster a sense of community. When Calandrelli asked Lockheed about this decision, the company confirmed it had “paused” these resource group activities to “align with the new executive order.”

An unwelcoming environment

For women and minorities, Calandrelli said, this creates an unwelcoming environment.

“You want to go where you are celebrated and wanted, not where you are tolerated,” she said. “That sense of belonging is going to take a hit. It’s going to be harder to recruit women and keep women.”

This is not just a problem for women and minorities, but for everyone, Calandrelli said. The aerospace industry is competing with others for top engineering talent. Prospective engineers who feel unwanted in aerospace, as well as women and minorities working for space companies today, may find the salary and environment more welcoming at Apple or Google or elsewhere in the tech industry. That’s a problem for the US Space Force and other areas of the government seeking to ensure the US space industry retains its lead in satellite technology, launch, communications and other aspects of space that touch every part of life on Earth.

What happens when DEI becomes DOA in the aerospace industry? Read More »

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In one dog breed, selection for utility may have selected for obesity

behavior, Biology, Dogs, Genetics, Labrador retriever, Science / /

High-risk Labradors also tended to pester their owners for food more often. Dogs with low genetic risk scores, on the other hand, stayed slim regardless of whether the owners paid attention to how and whether they were fed or not.

But other findings proved less obvious. “We’ve long known chocolate-colored Labradors are prone to being overweight, and I’ve often heard people say that’s because they’re really popular as pets for young families with toddlers that throw food on the floor all the time and where dogs are just not given that much attention,” Raffan says. Her team’s data showed that chocolate Labradors actually had a much higher genetic obesity risk than yellow or black ones

Some of the Labradors particularly prone to obesity, the study found, were guide dogs, which were included in the initial group. Training a guide dog in the UK usually takes around two years, during which the dogs learn multiple skills, like avoiding obstacles, stopping at curbs, navigating complex environments, and responding to emergency scenarios. Not all dogs are able to successfully finish this training, which is why guide dogs are often selectively bred with other guide dogs in the hope their offspring would have a better chance at making it through the same training.

But it seems that this selective breeding among guide dogs might have had unexpected consequences. “Our results raise the intriguing possibility that we may have inadvertently selected dogs prone to obesity, dogs that really like their food, because that makes them a little bit more trainable. They would do anything for a biscuit,” Raffan says.

The study also found that genes responsible for obesity in dogs are also responsible for obesity in humans. “The impact high genetic risk has on dogs leads to increased appetite. It makes them more interested in food,” Raffan claims. “Exactly the same is true in humans. If you’re at high genetic risk you aren’t inherently lazy or rubbish about overeating—it’s just you are more interested in food and get more reward from it.”

Science, 2025.  DOI: 10.1126/science.ads2145

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openai-pushes-ai-agent-capabilities-with-new-developer-api

OpenAI pushes AI agent capabilities with new developer API

AI, AI agents, Biz & IT, chatgpt, chatgtp, Computer-Using Agent, large language models, machine learning, openai, Operator, Tech / /

Developers using the Responses API can access the same models that power ChatGPT Search: GPT-4o search and GPT-4o mini search. These models can browse the web to answer questions and cite sources in their responses.

That’s notable because OpenAI says the added web search ability dramatically improves the factual accuracy of its AI models. On OpenAI’s SimpleQA benchmark, which aims to measure confabulation rate, GPT-4o search scored 90 percent, while GPT-4o mini search achieved 88 percent—both substantially outperforming the larger GPT-4.5 model without search, which scored 63 percent.

Despite these improvements, the technology still has significant limitations. Aside from issues with CUA properly navigating websites, the improved search capability doesn’t completely solve the problem of AI confabulations, with GPT-4o search still making factual mistakes 10 percent of the time.

Alongside the Responses API, OpenAI released the open source Agents SDK, providing developers free tools to integrate models with internal systems, implement safeguards, and monitor agent activities. This toolkit follows OpenAI’s earlier release of Swarm, a framework for orchestrating multiple agents.

These are still early days in the AI agent field, and things will likely improve rapidly. However, at the moment, the AI agent movement remains vulnerable to unrealistic claims, as demonstrated earlier this week when users discovered that Chinese startup Butterfly Effect’s Manus AI agent platform failed to deliver on many of its promises, highlighting the persistent gap between promotional claims and practical functionality in this emerging technology category.

OpenAI pushes AI agent capabilities with new developer API Read More »

how-whale-urine-benefits-the-ocean-ecosystem

How whale urine benefits the ocean ecosystem

Biology, Ecology, marine animals, marine ecology, Science, whales / /

A “great whale conveyor belt”

illustration showing how whale urine spreads throughout the ocean ecosystem

Credit: A. Boersma

Migrating whales typically gorge in summers at higher latitudes to build up energy reserves to make the long migration to lower latitudes. It’s still unclear exactly why the whales migrate, but it’s likely that pregnant females in particular find it more beneficial to give birth and nurse their young in warm, shallow, sheltered areas—perhaps to protect their offspring from predators like killer whales. Warmer waters also keep the whale calves warm as they gradually develop their insulating layers of blubber. Some scientists think that whales might also migrate to molt their skin in those same warm, shallow waters.

Roman et al. examined publicly available spatial data for whale feeding and breeding grounds, augmented with sightings from airplane and ship surveys to fill in gaps in the data, then fed that data into their models for calculating nutrient transport. They focused on six species known to migrate seasonally over long distances from higher latitudes to lower latitudes: blue whales, fin whales, gray whales, humpback whales, and North Atlantic and southern right whales.

They found that whales can transport some 4,000 tons of nitrogen each year during their migrations, along with 45,000 tons of biomass—and those numbers could have been three times larger in earlier eras before industrial whaling depleted populations. “We call it the ‘great whale conveyor belt,’” Roman said. “It can also be thought of as a funnel, because whales feed over large areas, but they need to be in a relatively confined space to find a mate, breed, and give birth. At first, the calves don’t have the energy to travel long distances like the moms can.” The study did not include any effects from whales releasing feces or sloughing their skin, which would also contribute to the overall nutrient flux.

“Because of their size, whales are able to do things that no other animal does. They’re living life on a different scale,” said co-author Andrew Pershing, an oceanographer at the nonprofit organization Climate Central. “Nutrients are coming in from outside—and not from a river, but by these migrating animals. It’s super-cool, and changes how we think about ecosystems in the ocean. We don’t think of animals other than humans having an impact on a planetary scale, but the whales really do.” 

Nature Communications, 2025. DOI: 10.1038/s41467-025-56123-2  (About DOIs).

How whale urine benefits the ocean ecosystem Read More »

what-the-epa’s-“endangerment-finding”-is-and-why-it’s-being-challenged

What the EPA’s “endangerment finding” is and why it’s being challenged

climate change, Earth science, EPA, greenhouse gasses, Policy, Science, trump administration / /

Getting rid of the justification for greenhouse gas regulations won’t be easy.

Credit: Mario Tama/Getty Images

A document that was first issued in 2009 would seem an unlikely candidate for making news in 2025. Yet the past few weeks have seen a steady stream of articles about an analysis first issued by the Environmental Protection Agency (EPA) in the early years of Obama’s first term: the endangerment finding on greenhouse gasses.

The basics of the document are almost mundane: greenhouse gases are warming the climate, and this will have negative consequences for US citizens. But it took a Supreme Court decision to get written in the first place, and it has played a role in every attempt by the EPA to regulate greenhouse gas emissions across multiple administrations. And, while the first Trump administration left it in place, the press reports we’re seeing suggest that an attempt will be made to eliminate it in the near future.

The only problem: The science in which the endangerment finding is based on is so solid that any ensuing court case will likely leave its opponents worse off in the long run, which is likely why the earlier Trump administration didn’t challenge it.

Get comfortable, because the story dates all the way back to the first Bush administration.

A bit of history

One of the goals of the US’s Clean Air Act, first passed in 1963, is to “address the public health and welfare risks posed by certain widespread air pollutants.” By the end of the last century, it was becoming increasingly clear that greenhouse gases fit that definition. While they weren’t necessarily directly harmful to the people inhaling them—our lungs are constantly being filled with carbon dioxide, after all—the downstream effects of the warming they caused could certainly impact human health and welfare. But, with the federal government taking no actions during George W. Bush’s time in office, a group of states and cities sued to force the EPA’s hand.

That suit eventually reached the Supreme Court in the form of Massachusetts v. EPA, which led to a ruling in 2007 determining that the Clean Air Act required the EPA perform an analysis of the dangers posed by greenhouse gasses. That analysis was done by late 2007, but the Bush administration simply ignored it for the remaining year it had in office. (It was eventually released after Bush left office.)

That left the Obama-era EPA to reach essentially the same conclusions that the Bush administration had: greenhouse gasses are warming the planet. And that will have various impacts—sea level rise, dangerous heat, damage to agriculture and forestry, and more.

That conclusion compelled the EPA to formulate regulations to limit the emission of greenhouse gasses from power plants. Obama’s EPA did just that, but came late enough to still be tied up in courts by the time his term ended. They were also formulated before the plunge in the cost of renewable power sources, which have since led to a drop in carbon emissions that have far outpaced what the EPA’s rules intended to accomplish.

The first Trump administration formulated alternative rules that also ended up in court for being an insufficient response to the conclusions of the endangerment finding. Which ultimately led the Biden administration to start formulating a new set of rules. And at that point, the Supreme Court decided to step in and rule on the Obama rules, even though everyone knew they would never go into effect.

The court indicated that the EPA needed to regulate each power plant individually, rather than regulating the wider grid, which sent the Biden administration back to the drawing board. Its attempts at crafting regulations were also in court when Trump returned to office.

There were a couple of notable aspects to that last case, West Virginia v. EPA, which hinged on the fact that Congress had never explicitly indicated that it wanted to see greenhouse gasses regulated. Congress responded by ensuring that the Inflation Reduction Act’s energy-focused components specifically mentioned that these were intended to limit carbon emissions, eliminating one potential roadblock. The other thing is that, in this and other court cases, the Supreme Court could have simply overturned Massachusetts v. EPA, the case that put greenhouse gasses within the regulatory framework of the Clean Air Act. Yet a court that has shown a great enthusiasm for overturning precedent didn’t do so.

Nothing dangerous?

So, in the 15 years since the EPA initially released its endangerment findings, they’ve resulted in no regulations whatsoever. But, as long as they existed, the EPA is required to at least attempt to regulate them. So, getting rid of the endangerment findings would seem like the obvious thing for an administration led by a president who repeatedly calls climate change a hoax. And there were figures within the first Trump administration who argued in favor of that.

So why didn’t it happen?

That was never clear, but I’d suggest at least some members of the first Trump administration were realistic about the likely results. The effort to contest the endangerment finding was pushed by people who largely reject the vast body of scientific evidence that indicates that greenhouse gases are warming the climate. And, if anything, the evidence had gotten more decisive in the years between the initial endangerment finding and Trump’s inauguration. I expect that their effort was blocked by people who knew that it would fail in the courts, and likely leave behind precedents that made future regulatory efforts easier.

This interpretation is supported by the fact that the Trump-era EPA received a number of formal petitions to revisit the endangerment finding. Having read a few (something you should not do), they are uniformly awful. References to supposed peer-reviewed “papers” turn out to be little more than PDFs hosted on a WordPress site. Other arguments are based on information contained in the proceedings of a conference organized by an anti-science think tank. The Trump administration rejected them all with minimal comment the day before Biden’s inauguration.

Biden’s EPA went back and made detailed criticisms of each of them if you want to see just how laughable the arguments against mainstream science were at the time. And, since then, we’ve experienced a few years of temperatures that are so high they’ve surprised many climate scientists.

Unrealistic

But the new head of the EPA is apparently anything but a realist, and multiple reports have indicated he’s asking to be given the opportunity to go ahead and redo the endangerment finding. A more recent report suggests two possibilities. One is to recruit scientists from the fringes to produce a misleading report and roll the dice on getting a sympathetic judge who will overlook the obvious flaws. The other would be to argue that any climate change that happens will have net benefits to the US.

That latter approach would run into the problem that we’ve gotten increasingly sophisticated at doing analyses that attribute the impact of climate change on the individual weather disasters that do harm the welfare of citizens of the US. While it might have been possible to make a case for uncertainty here a decade ago, that window has been largely closed by the scientific community.

Even if all of these efforts fail, it will be entirely possible for the EPA to construct greenhouse gas regulations that accomplish nothing and get tied up in court for the remainder of Trump’s term. But a court case could show just how laughably bad the positions staked out by climate contrarians are (and, by extension, the position of the president himself). There’s a small chance that the resulting court cases will result in a legal record that will make it that much harder to accept the sorts of minimalist regulations that Trump proposed in his first term.

Which is probably why this approach was rejected the first time around.

Photo of John Timmer

John is Ars Technica’s science editor. He has a Bachelor of Arts in Biochemistry from Columbia University, and a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. When physically separated from his keyboard, he tends to seek out a bicycle, or a scenic location for communing with his hiking boots.

What the EPA’s “endangerment finding” is and why it’s being challenged Read More »

firmware-update-bricks-hp-printers,-makes-them-unable-to-use-hp-cartridges

Firmware update bricks HP printers, makes them unable to use HP cartridges

HP, printers, Tech / /

HP, along with other printer brands, is infamous for issuing firmware updates that brick already-purchased printers that have tried to use third-party ink. In a new form of frustration, HP is now being accused of issuing a firmware update that broke customers’ laser printers—even though the devices are loaded with HP-brand toner.

The firmware update in question is version 20250209, which HP issued on March 4 for its LaserJet MFP M232-M237 models. Per HP, the update includes “security updates,” a “regulatory requirement update,” “general improvements and bug fixes,” and fixes for IPP Everywhere. Looking back to older updates’ fixes and changes, which the new update includes, doesn’t reveal anything out of the ordinary. The older updates mention things like “fixed print quality to ensure borders are not cropped for certain document types,” and “improved firmware update and cartridge rejection experiences.” But there’s no mention of changes to how the printers use or read toner.

However, users have been reporting sudden problems using HP-brand toner in their M232–M237 series printers since their devices updated to 20250209. Users on HP’s support forum say they see Error Code 11 and the hardware’s toner light flashing when trying to print. Some said they’ve cleaned the contacts and reinstalled their toner but still can’t print.

“Insanely frustrating because it’s my small business printer and just stopped working out of nowhere[,] and I even replaced the tone[r,] which was a $60 expense,” a forum user wrote on March 8.

Firmware update bricks HP printers, makes them unable to use HP cartridges Read More »

maserati-kills-electric-version-of-mc20-supercar-for-lack-of-demand

Maserati kills electric version of MC20 supercar for lack of demand

Cars, Maserati MC20 / /

Electric motors are, in so many ways, much better than internal combustion engines. They don’t waste most of the energy you put into them as heat and sound, they’re easy to control, and they make huge amounts of torque almost instantly. Having recently driven BMW’s 430i and i4 back to back over the course of two weeks, the electric version was easier in traffic and more responsive on a twisty road. Electric wins, then. Except at the very high end, it seems.

Because even though electric motors can pack a punch, people paying big money for super- and hypercars are increasingly disinterested in those cars being electrified. So much so that Maserati has canceled the all-electric version of the MC20.

The MC20 debuted in 2020. No longer associated with Ferrari after that brand was spun out and IPO’d, the MC20 could offer a full carbon-fiber monocoque and an engine with very clever F1-derived combustion technology, undercutting its now-independent Italian competitor to the tune of more than $100,000 in the process.

Maserati kills electric version of MC20 supercar for lack of demand Read More »

the-starship-program-hits-another-speed-bump-with-second-consecutive-failure

The Starship program hits another speed bump with second consecutive failure

Commercial space, elon musk, launch, NASA, Science, Space, spacex, starship, starship flight 8 / /

The flight plan going into Thursday’s mission called for sending Starship on a journey halfway around the world from Texas, culminating in a controlled reentry over the Indian Ocean before splashing down northwest of Australia.

The test flight was supposed to be a do-over of the previous Starship flight on January 16, when the rocket’s upper stage—itself known as Starship, or ship—succumbed to fires fueled by leaking propellants in its engine bay. Engineers determined the most likely cause of the propellant leak was a harmonic response several times stronger than predicted, suggesting the vibrations during the ship’s climb into space were in resonance with the vehicle’s natural frequency. This would have intensified the vibrations beyond the levels engineers expected.

The Super Heavy booster returned to Starbase in Texas to be caught back at the launch pad. Credit: SpaceX

Engineers test-fired the Starship vehicle earlier this month for this week’s test flight, validating changes to propellant temperatures, operating thrust, and the ship’s fuel feed lines leading to its six Raptor engines.

But engineers missed something. On Thursday, the Raptor engines began shutting down on Starship about eight minutes into the flight, and the rocket started tumbling 90 miles (146 kilometers) over the southeastern Gulf of Mexico. SpaceX ground controllers lost all contact with the rocket about nine-and-a-half minutes after liftoff.

“Prior to the end of the ascent burn, an energetic event in the aft portion of Starship resulted in the loss of several Raptor engines,” SpaceX wrote on X. “This in turn led to a loss of attitude control and ultimately a loss of communications with Starship.”

Just like in January, residents and tourists across the Florida peninsula, the Bahamas, and the Turks and Caicos Islands shared videos of fiery debris trails appearing in the twilight sky. Air traffic controllers diverted or delayed dozens of commercial airline flights flying through the debris footprint, just as they did in response to the January incident.

There were no immediate reports Thursday of any Starship wreckage falling over populated areas. In January, residents in the Turks and Caicos Islands recovered small debris fragments, including one piece that caused minor damage when it struck a car. The debris field from Thursday’s failed flight appeared to fall west of the areas where debris fell after Starship Flight 7.

A spokesperson for the Federal Aviation Administration said the regulatory agency will require SpaceX to perform an investigation into Thursday’s Starship failure.

The Starship program hits another speed bump with second consecutive failure Read More »

nearly-1-million-windows-devices-targeted-in-advanced-“malvertising”-spree

Nearly 1 million Windows devices targeted in advanced “malvertising” spree

Biz & IT, maltertising, malware, microsoft, Security / /

A broad overview of the four stages. Credit: Microsoft

The campaign targeted “nearly” 1 million devices belonging both to individuals and a wide range of organizations and industries. The indiscriminate approach indicates the campaign was opportunistic, meaning it attempted to ensnare anyone, rather than targeting certain individuals, organizations, or industries. GitHub was the platform primarily used to host the malicious payload stages, but Discord and Dropbox were also used.

The malware located resources on the infected computer and sent them to the attacker’s c2 server. The exfiltrated data included the following browser files, which can store login cookies, passwords, browsing histories, and other sensitive data.

  • AppDataRoamingMozillaFirefoxProfiles.default-releasecookies.sqlite
  • AppDataRoamingMozillaFirefoxProfiles.default-releaseformhistory.sqlite
  • AppDataRoamingMozillaFirefoxProfiles.default-releasekey4.db
  • AppDataRoamingMozillaFirefoxProfiles.default-releaselogins.json
  • AppDataLocalGoogleChromeUser DataDefaultWeb Data
  • AppDataLocalGoogleChromeUser DataDefaultLogin Data
  • AppDataLocalMicrosoftEdgeUser DataDefaultLogin Data

Files stored on Microsoft’s OneDrive cloud service were also targeted. The malware also checked for the presence of cryptocurrency wallets including Ledger Live, Trezor Suite, KeepKey, BCVault, OneKey, and BitBox, “indicating potential financial data theft,” Microsoft said.

Microsoft said it suspects the sites hosting the malicious ads were streaming platforms providing unauthorized content. Two of the domains are movies7[.]net and 0123movie[.]art.

Microsoft Defender now detects the files used in the attack, and it’s likely other malware defense apps do the same. Anyone who thinks they may have been targeted can check indicators of compromise at the end of the Microsoft post. The post includes steps users can take to prevent falling prey to similar malvertising campaigns.

Nearly 1 million Windows devices targeted in advanced “malvertising” spree Read More »

intuitive-machines’-second-attempt-to-land-on-the-moon-also-went-sideways

Intuitive Machines’ second attempt to land on the Moon also went sideways

clps, intuitive machines, NASA, Space / /

Inside a small control room, during the middle of the day on Thursday local time in Texas, about a dozen white-knuckled engineers at a space startup named Intuitive Machines started to get worried. Their spacecraft, a lander named Athena, was beginning its final descent down to the lunar surface.

A little more than a year had passed since the company’s first attempt to land on the Moon with a similarly built vehicle, Odysseus. Due to problems with that spacecraft’s laser rangefinder, it skidded into the Moon’s surface and toppled over.

So engineers at Intuitive Machines had checked, and re-checked the laser-based altimeters on Athena. When the lander got down within about 30 km of the lunar surface, they tested the rangefinders again. Worryingly, there was some noise in the readings as the laser bounced off the Moon. However, the engineers had reason to believe that, maybe, the readings would improve as the spacecraft got nearer to the surface.

“Our hope was that the signal to noise would improve as we got closer to the Moon,” said Tim Crain, chief technology officer for Intuitive Machines, speaking to reporters afterward.

It didn’t. The noise remained. And so, to some extent, Athena went down to the Moon blind. The spacecraft’s propulsion system, based on liquid oxygen and methane, and designed in-house, worked beautifully. But in the final moments, the spacecraft did not quite know where it was relative to the surface.

Probably lying on its side

Beyond that, Crain and the rest of the company, including its chief executive Steve Altemus, could not precisely say what happened. After Athena landed, the engineers in mission control could talk to the spacecraft, and they were able to generate some power from its solar arrays. But precisely where it was, or how it lay on the ground, they could not say a few hours later.

Based on a reading from an inertial measurement unit inside the vehicle, most likely Athena is lying on its side. This is the same fate Odysseus met last year, when it skidded into the Moon, broke a leg, and toppled over.

Intuitive Machines’ second attempt to land on the Moon also went sideways Read More »

starlink-benefits-as-trump-admin-rewrites-rules-for-$42b-grant-program

Starlink benefits as Trump admin rewrites rules for $42B grant program

access, and Deployment program, BEAD program, Broadband Equity, elon musk, Policy, starlink / /

Don’t be “technology-blind,” broadband group says

The Benton Institute for Broadband & Society criticized what it called “Trump’s BEAD meddling,” saying it would “leave millions of Americans with broadband that is slower, less reliable, and more expensive.” The shift to a “technology-neutral” approach should not be “technology-blind,” the advocacy group said.

“Fiber broadband is widely understood to be better than other Internet options—like Starlink’s satellites—because it delivers significantly faster speeds, is more reliable due to its resistance to interference (from weather, foliage, terrain, etc), has higher bandwidth capacity, and offers symmetrical upload and download speeds, making it ideal for activities like telehealth, online learning, streaming, and gaming that require consistent high performance,” the group said.

It’s ultimately up to individual states to distribute funds to ISPs after getting their allocations from the US government, though the states have to follow rules issued by federal officials. No one knows exactly how much each Internet provider will receive, but a Wall Street Journal report this week said the new rules could help Starlink get nearly half of the available funding.

“Under the BEAD program’s original rules, Starlink was expected to get up to $4.1 billion, said people familiar with the matter. With Lutnick’s overhaul, Starlink, a unit of Musk’s SpaceX, could receive $10 billion to $20 billion, they said,” according to the WSJ report.

The end of BEAD’s fiber preference would also help cable and fixed wireless providers access grant funding. Lobby groups for those industries have been calling for rule changes to help their members obtain grants.

While the Commerce Department is moving ahead with BEAD changes on its own, Republicans are also proposing a rewrite of the law. House Communications and Technology Subcommittee Chairman Richard Hudson (R-N.C.) yesterday announced legislation that his office said would eliminate “burdensome conditions imposed by the Biden-Harris Administration, including those related to labor, climate change, and rate regulation, that made deployment more expensive and participation less attractive.”

Starlink benefits as Trump admin rewrites rules for $42B grant program Read More »

norovirus-vaccine-hints-at-defusing-explosive-stomach-bug-in-early-trial

Norovirus vaccine hints at defusing explosive stomach bug in early trial

health, Norovirus, Science, vaccine, vaxart / /

Phase I study showed vaccine was safe and spurred immune responses in older people.

An electron micrograph of norovirus. Credit: Getty| BSIP

In an early clinical trial, an experimental norovirus vaccine given as a pill produced defensive responses exactly where it counts—in the saliva of older people most vulnerable to the explosive stomach bug.

The results, published this week in Science Translational Medicine, are another step in the long effort to thwart the gruesome germ, which finds a way to violently hollow out innards wherever people go—from restaurants to natural wonders and even the high seas. It’s a robust, extremely infectious virus that spreads via the nauseating fecal-oral route. Infected people spew billions of virus particles in their vomit and diarrhea, and shedding can last weeks. The particles aren’t easily killed by hand sanitizers and can linger on surfaces for up to two weeks. Exposure to as few as 10 virus particles can spark an infection. According to the Centers for Disease Control and Prevention, norovirus causes an average of between 19 and 21 million cases of acute gastroenteritis in the US every year, leading to 109,000 hospitalizations and 900 deaths. This racks up an economic burden estimated to be $2 billion to $10.6 billion.

Vaccine design

For most, the gut-busting bug is miserable but usually over in a few days. But older people—especially those with underlying medical conditions—are vulnerable to severe outcomes. About 90 percent of people who die from a norovirus infection are people age 65 or older who live in long-term care facilities.

For this reason, researchers have aimed to design a vaccine that’s sure to be effective in older people, who typically have weaker immune responses just from the aging process. But, of course, this makes the already daunting task of developing a vaccine yet harder—and norovirus poses some specific challenges. For one, there aren’t a lot of good laboratory models and animal systems to run norovirus experiments or test candidate drugs. For example, healthy mice infected with a mouse version of norovirus don’t develop any symptoms (lucky critters). Then there’s the fact that norovirus isn’t one virus; it’s many. There are 49 different genotypes of norovirus, which have been categorized into 10 “genogroups.” It’s unclear if protection against one genotype or genogroup will help protect against the others, and if so, by how much.

Currently, there are several norovirus vaccines in the works, at various stages with various designs. The one published this week is being developed by a San Francisco-based company called Vaxart and uses a proprietary oral delivery system. The pill includes a deactivated virus particle (an adenovirus), which can’t replicate in people but can deliver the genetic blueprints of two molecules into cells lining our intestines. One of the genetic blueprints it delivers tells the intestinal cells how to manufacture a protein found on the outside of norovirus particles, called VP.1. Once manufactured in the intestines, VP.1 can train the immune system to identify invading norovirus particles and attack them. The other genetic code included in the vaccine is for what’s called an “adjuvant,” which is basically a booster molecule that helps rev up immune responses.

While several other vaccines in the works are delivered by injections, producing systemic responses, the idea of the pill is to build up immune responses to norovirus directly where it invades and attacks—the mucosal lining of the digestive tract, including the mouth and intestines. There is some preliminary data suggesting that having antibodies against norovirus in saliva correlates with protection from the virus.

Good news

Vaxart has previously published Phase I trial data showing that its pill is safe and well-tolerated in healthy adults ages 18 to 49. The study, published in 2018, also indicated that the pill generated “substantial” systemic and mucosal antibodies against norovirus.

For the new study, Vaxart did a repeat Phase I trial with 65 older people—ages 55 to 80, broken into groups of 55 to 65, and 66 to 80. The participants were randomly assigned to get either a placebo (22) or a low (16), medium (16), or high (11) dose of the vaccine VXA-G1.1-NN, which targets one genotype of norovirus. Again, the vaccine was safe and well-tolerated. There were no serious side effects. The most common side effects were headache and fatigue, which were reported at about the same rates among the placebo and vaccinated groups.

Further, detailed examination of the participants’ immune responses showed not only systemic response, but responses in distant mucus membranes. In the blood, two types of antibodies (IgA and IgG) increased by several fold after vaccination compared with the placebo group. The group with the largest responses was the one that received the high dose.

A test that acts as a surrogate for neutralizing antibody responses to norovirus indicated that the antibodies spurred by the vaccine could block the virus. Additional tests found that cellular immune responses were also activated and that the systemic responses result in protection in places far from the intestines—namely the mouth and nose. Saliva tests and nasal swabs found significant jumps in secreted IgA against norovirus.

Immune responses were strongest in the first two months after vaccination and diminished over time, but some persisted for nearly seven months. When the scientists looked at differences between the two age groups (55–65 and 65–80), they didn’t see significant differences, suggesting the vaccine was equally effective in the older group.

Overall, the scientists at Vaxart concluded that the vaccine “has the potential to inhibit infection, viral shedding, and transmission.”

“Overall, VXA-G1.1-NN administration in older adults led to robust and durable immunogenicity detected both in circulation and multiple mucosal sites, an exciting outcome considering that diminished cellular and mucosal immunity are typical in older populations,” they wrote.

Not so good news

The outlook isn’t entirely rosy, though—there is some bad news. While immune responses rose in statistically significant measures during this small early-stage trial, it’s unclear if that equates to real-life protection. And there’s some good reason to be wary. In 2023, Vaxart released results of a challenge study, in which 141 brave souls (76 vaccinated and 65 given a placebo) were deliberately exposed to norovirus to see if the vaccine was protective. The results were weak: 53 placebo-group members (81.5 percent) became infected with norovirus, as determined by a PCR test looking for genetic evidence of the virus in their stool—and so did 76 vaccinated people (60 percent). That worked out to the vaccine offering only a 29 percent lower relative risk of getting infected. Looking at whether infected people developed symptoms of acute gastroenteritis, the vaccine had a protective efficacy of about 21 percent: 34 vaccinated people (48 percent) versus 37 placebo-group members (57 percent) developed symptoms.

While the study was a disappointment, Vaxart wasn’t ready to give up, arguing that the challenge study used large-dose exposures that people wouldn’t encounter in the real world.

“We use lots of copies of virus to ensure a high infection rate. In nature, 10 to 15 copies of virus is generally enough to give certain susceptible individuals disease,” James Cummings, chief medical officer at Vaxart, said in an investor call reported by Fierce Biotech at the time. “Field efficacy generally goes up, because the amount of inoculum that is causing disease that will be seen in the field is far lower than what is seen in the challenge study. My projection is that we would see an improvement in the decrease of [acute gastroenteritis] with our vaccine.”

Even a slight boost in efficacy could make the vaccine seem worthwhile. A 2012 modeling study suggested that even a vaccine with 50 percent efficacy could avert up to 2.2 million cases and save up to $2 billion over four years.

For now, we’ll have to wait to see what future trial data shows. And Vaxart’s vaccine isn’t the only one in the pipeline, nor is it the furthest along. Moderna has a norovirus vaccine in a Phase 3 trial, which is a larger study that will look at efficacy. But, while the trial is just beginning, Moderna noted in a financial update in February that the trial has been put on hold by the Food and Drug Administration due to a possible neurological side effect in one participant.

“The trial is currently on FDA clinical hold following a single adverse event report of a case of Guillain-Barré syndrome, which is currently under investigation,” Moderna reported. “The Company does not expect an impact on the study’s efficacy readout timeline as enrollment in the Northern Hemisphere has already been completed. The timing of the Phase 3 readout will be dependent on case accruals.”

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Beth is Ars Technica’s Senior Health Reporter. Beth has a Ph.D. in microbiology from the University of North Carolina at Chapel Hill and attended the Science Communication program at the University of California, Santa Cruz. She specializes in covering infectious diseases, public health, and microbes.

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