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Apr 18 2024 KFF Health News

A team of Montana researchers is playing a key role in the development of a more effective vaccine against tuberculosis, an infectious disease that has killed more people than any other.

The BCG (Bacille Calmette-Guérin) vaccine, created in 1921, remains the sole TB vaccine. While it is 40% to 80% effective in young children, its efficacy is very low in adolescents and adults, leading to a worldwide push to create a more powerful vaccine.

One effort is underway at the University of Montana Center for Translational Medicine. The center specializes in improving and creating vaccines by adding what are called novel adjuvants. An adjuvant is a substance included in the vaccine, such as fat molecules or aluminum salts, that enhances the immune response, and novel adjuvants are those that have not yet been used in humans. Scientists are finding that adjuvants make for stronger, more precise, and more durable immunity than antigens, which create antibodies, would alone.

Eliciting specific responses from the immune system and deepening and broadening the response with adjuvants is known as precision vaccination. "It's not one-size-fits-all," said Ofer Levy, a professor of pediatrics at Harvard University and the head of the Precision Vaccines Program at Boston Children's Hospital. "A vaccine might work differently in a newborn versus an older adult and a middle-aged person."

The ultimate precision vaccine, said Levy, would be lifelong protection from a disease with one jab. "A single-shot protection against influenza or a single-shot protection against covid, that would be the holy grail," Levy said.

Jay Evans, the director of the University of Montana center and the chief scientific and strategy officer and a co-founder of Inimmune, a privately held biotechnology company in Missoula, said his team has been working on a TB vaccine for 15 years. The private-public partnership is developing vaccines and trying to improve existing vaccines, and he said it's still five years off before the TB vaccine might be distributed widely.

It has not gone unnoticed at the center that this state-of-the-art vaccine research and production is located in a state that passed one of the nation's most extreme anti-vaccination laws during the pandemic in 2021. The law prohibits businesses and governments from discriminating against people who aren't vaccinated against covid-19 or other diseases, effectively banning both public and private employers from requiring workers to get vaccinated against covid or any other disease. A federal judge later ruled that the law cannot be enforced in health care settings, such as hospitals and doctors' offices.

In mid-March, the Bill & Melinda Gates Medical Research Institute announced it had begun the third and final phase of clinical trials for the new vaccine in seven countries. The trials should take about five years to complete. Research and production are being done in several places, including at a manufacturing facility in Hamilton owned by GSK, a giant pharmaceutical company.

Known as the forgotten pandemic, TB kills up to 1.6 million people a year, mostly in impoverished areas in Asia and Africa, despite its being both preventable and treatable. The U.S. has seen an increase in tuberculosis over the past decade, especially with the influx of migrants, and the number of cases rose by 16% from 2022 to 2023. Tuberculosis is the leading cause of death among people living with HIV, whose risk of contracting a TB infection is 20 times as great as people without HIV.

"TB is a complex pathogen that has been with human beings for ages," said Alemnew Dagnew, who heads the program for the new vaccine for the Gates Medical Research Institute. "Because it has been with human beings for many years, it has evolved and has a mechanism to escape the immune system. And the immunology of TB is not fully understood." Related StoriesNigeria first to rollout new Men5CV vaccine against meningitisChatGPT could be an effective tool to help reduce vaccine hesitancyPersonalized anti-tumor vaccine enhances immunotherapy for liver cancer

The University of Montana Center for Translational Medicine and Inimmune together have 80 employees who specialize in researching a range of adjuvants to understand the specifics of immune responses to different substances. "You have to tailor it like tools in a toolbox towards the pathogen you are vaccinating against," Evans said. "We have a whole library of adjuvant molecules and formulations."

Vaccines are made more precise largely by using adjuvants. There are three basic types of natural adjuvants: aluminum salts; squalene, which is made from shark liver; and some kinds of saponins, which are fat molecules. It's not fully understood how they stimulate the immune system. The center in Missoula has also created and patented a synthetic adjuvant, UM-1098, that drives a specific type of immune response and will be added to new vaccines.

One of the most promising molecules being used to juice up the immune system response to vaccines is a saponin molecule from the bark of the quillay tree, gathered in Chile from trees at least 10 years old. Such molecules were used by Novavax in its covid vaccine and by GSK in its widely used shingles vaccine, Shingrix. These molecules are also a key component in the new tuberculosis vaccine, known as the M72 vaccine.

But there is room for improvement.

"The vaccine shows 50% efficacy, which doesn't sound like much, but basically there is no effective vaccine currently, so 50% is better than what's out there," Evans said. "We're looking to take what we learned from that vaccine development with additional adjuvants to try and make it even better and move 50% to 80% or more."

By contrast, measles vaccines are 95% effective.

According to Medscape, around 15 vaccine candidates are being developed to replace the BCG vaccine, and three of them are in phase 3 clinical trials.

One approach Evans' center is researching to improve the new vaccine's efficacy is taking a piece of the bacterium that causes TB, synthesizing it, and combining it with the adjuvant QS-21, made from the quillay tree. "It stimulates the immune system in a way that is specific to TB and it drives an immune response that is even closer to what we get from natural infections," Evans said.

The University of Montana center is researching the treatment of several problems not commonly thought of as treatable with vaccines. They are entering the first phase of clinical trials for a vaccine for allergies, for instance, and first-phase trials for a cancer vaccine. And later this year, clinical trials will begin for vaccines to block the effects of opioids like heroin and fentanyl. The University of Montana received the largest grant in its history, $33 million, for anti-opioid vaccine research. It works by creating an antibody that binds with the drug in the bloodstream, which keeps it from entering the brain and creating the high.

For now, though, the eyes of health care experts around the world are on the trials for the new TB vaccines, which, if they are successful, could help save countless lives in the world's poorest places.

This article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism. Source:

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Angels star Trout needs surgery for torn meniscus

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Angels star Trout needs surgery for torn meniscus

ANAHEIM, Calif. — Angels superstar Mike Trout, hoping for a fully healthy season after being significantly limited by injury the past three years, needs knee surgery, general manager Perry Minasian said Tuesday.

Trout has a torn meniscus in his left knee, Minasian said.

The procedure, which is believed to be scheduled for Friday, isn’t considered to be season-ending. A source familiar with Trout’s injury said a four- to six-week timetable is a best-case scenario, but a true timeline won’t be established until doctors take a closer look.

“It’s just frustrating, but we’ll get through it,” an emotional Trout said in the clubhouse.

Trout played the entire game Monday, a come-from-behind 6-5 victory over the Philadelphia Phillies, and even stole a base.

Trout said he wasn’t sure when he sustained the tear but that he felt an ache in his knee when running in from the third inning. The soreness wasn’t persistent during the game but his knee ached all night, and he underwent an MRI on Tuesday morning that revealed the tear.

Trout, 32, finished first or second in MVP voting seven of eight years from 2012 to 2019, putting him on a path to becoming possibly the greatest player in baseball history. But injuries robbed him of significant chunks of playing time coming off the COVID-shortened season of 2020.

Trout played in only 237 of a potential 486 games from 2021 to 2023, suffering injuries to his calf, back and hand. He entered the 2024 season reinvigorated, even hoping to run the bases more freely. Trout accomplished that through the Angels’ first 29 games, hitting a major league-leading 10 home runs but also stealing six bases, the same total he had from 2020 to 2023.

Now, though, he is faced with another injury rehab.

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Sources: Ohtani money went to bookie via casino

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Sources: Ohtani money went to bookie via casino

The series of $500,000 payments Ippei Mizuhara sent from Shohei Ohtani‘s bank account to an illegal bookmaking operation were forwarded to California and Las Vegas casinos, where the money was deposited in gambling accounts, converted to playing chips and later cashed out to pay the bookie, multiple sources with direct knowledge of the operation told ESPN.

The description of what happened to Ohtani’s money sheds new light on the ongoing federal probe that drew global attention after his interpreter, Mizuhara, was accused of stealing $16 million from the Los Angeles Dodgers slugger to feed what he has called a gambling addiction.

Mathew Bowyer, the California bookmaker who took Mizuhara’s bets, was a frequent customer at Las Vegas casino Resorts World. The sources told ESPN that Mizuhara paid his losses to Bowyer’s associate, who forwarded the money to his own “marker” accounts at Resorts World and Pechanga Resort Casino in Southern California. The men then withdrew chips from the marker account, gambled with them, and if they won, cashed out.

Bowyer, 49, lost $7.9 million at Resorts World from June 2022 to October 2023, according to multiple sources. After Bowyer’s home was raided by federal agents on Oct. 5, he was dubbed a known bookmaker and banned from entering casinos throughout the United States, according to sources with direct knowledge of the ban.

Neither Bowyer nor his associate has been named in any indictment unsealed to date.

Attorneys for both Bowyer and his associate declined to comment.

Multiple sources told ESPN that Resorts World is at the center of what federal authorities described in an affidavit as an investigation into “illegal sports bookmaking organizations operating in Southern California, and the laundering of the proceeds of these operations through casinos in Las Vegas.” Twelve people have been charged or convicted to date, and two Vegas casinos have agreed to pay fines, according to the affidavit. Resorts World was served a federal subpoena last August that sought, among other things, documents related to its anti-money laundering policies.

A spokesperson for Resorts World told ESPN the casino does not comment on ongoing legal matters. “Resorts World Las Vegas takes any suggestion of violations seriously and is cooperating with the ongoing investigation,” the spokesperson said.

Resorts World opened its doors to the public in 2021 under the leadership of Scott Sibella, who was MGM Grand’s president from 2011 until he left for Resorts World in 2019. Sibella pleaded guilty to charges that, as president of MGM Grand, he failed to file suspicious activity reports about another Southern California bookie, Wayne Nix.

Nix, a former minor league baseball player, awaits sentencing after pleading guilty to operating an illegal gambling business and filing a false tax return. His clients included NBA legend Scottie Pippen, former MLB All-Star Yasiel Puig and Maverick Carter, the longtime friend and business manager of NBA superstar LeBron James.

The Nevada Current reported that Resorts World received a federal grand jury subpoena in August seeking “documents relating to the Company’s Anti-Money Laundering policies, Know Your Customer practices, policies and practices relating to extensions of credit, comps or other benefits, use of promotional chips, and other customer transactions.”

In September, Resorts World fired Sibella for “violating company policies.”

On Oct. 5, federal agents raided Bowyer’s home, seizing computers, cell phones, jewelry, luxury handbags, a money counting machine, cash and chips from several casinos, according to search warrant documents obtained by ESPN.

Federal agents, according to the documents, were authorized to seize records that could show evidence of Bowyer committing federal crimes, including transmission of wagering information, operation of an illegal gambling business, structuring to evade reporting requirements, and laundering the proceeds of an illegal gambling business.

Multiple sources told ESPN that Bowyer, who has worked as a commodity broker and owns a Brazilian jiu jitsu studio, got into the bookmaking business more than 20 years ago. It became his primary source of income soon after the 2008 financial crisis, when he befriended bookmaker Owen Hanson, the former USC football player convicted of running an international drug trafficking, gambling and money laundering operation. Hanson went to federal prison on a 21-year sentence in 2017 but had his sentence reduced and was released in March.

Unlike sportsbooks, where customers have to front money, bookies allow people to bet on credit. Mizuhara, who was one of more than 600 bettors with Bowyer’s book, ran up a debt of $40.7 million, according to federal authorities.

In an interview about the Mizuhara investigation, which included several text exchanges between the interpreter and Bowyer, Tyler Hatcher, the Special Agent in Charge at IRS Criminal Investigation in Los Angeles, told ESPN that Bowyer’s behavior was “typical of bookies.”

“They’re salesmen, right?” he said. “Their job is to … try to get them to continue to play. That’s what I saw. Just another salesman continuing to say, ‘Oh, it’s okay.’ You know, ‘we’ll get it next time.'”

Hatcher would not discuss the investigation into Bowyer.

Bookmakers like Bowyer typically rely on agents, or sub-bookies, to find clients. According to a bookmaker who spoke on condition of anonymity, the agents are paid returns of anywhere from 10 to 50 percent of a losing bet, depending on the value of the client.

“It depends on the arrangement. I’ve had it where I give 10% regardless if they win or lose because I want the customer and he’s going to lose in the long run,” the bookmaker said.

In a state where sports betting is not legal, Bowyer is among a small group of bookmakers who compete with each other for business, but also work together, running credit checks on potential customers and flagging “sharps,” or professional gamblers, according to sources with firsthand knowledge of bookmaking operations.

“We cross-reference clients. We call each other,” the bookmaker said. “It’s a very small network of guys. There are only 10 big names in the business. Everyone else is an agent.”

Sources familiar with Bowyer’s operation told ESPN that Bowyer has a long history with casinos, which he uses both for business and pleasure.

Bowyer is known in Vegas as a “whale,” a high-stakes gambler unafraid to lose millions on the casino floor. He has a reputation of bringing anywhere between $250,000 to $1 million each visit, which was as often as two or three times a month, the sources said.

He often brought a small group of friends who, according to the sources, coordinated bets and consolidated their balances at the end of their trip.

Casino employees are required to file suspicious activity reports for red flag behavior or when they know or suspect that money for any transaction over $5,000 is derived from illegal activity.

Resorts World did not answer ESPN’s questions about whether Bowyer’s activities triggered any such reports.

Failure to file these reports is a federal crime, to which Sibella pleaded guilty as part of the Nix investigation. Sibella could face a maximum sentence of five years in prison and a $250,000 fine. His sentencing is scheduled for May 8 in Los Angeles.

According to multiple sources with direct knowledge, Bowyer, his wife, Nicole, and their small circle of associates began making regular trips to Resorts World after it opened in 2021. Bowyer dropped more than $800,000 in his first visit, the sources said.

In return, Bowyer and his group received high-end “comps” through his casino host, who earned money in commission based on how much they gambled. The comps included free food and beverage, golf, tickets to shows and sporting events, shopping sprees, hotel suites and promo chips.

Resorts World, where Sibella was then president, authorized Nicole Bowyer to replace Bowyer’s casino host, allowing the couple to recoup some of his losses through payments to his wife, the sources told ESPN.

Even before the current federal investigation into his bookmaking activities, Bowyer had been “86’d,” or banned, from Vegas casinos like MGM Grand, the Palazzo and the Venetian, according to the sources. The Palazzo and the Venetian later reinstated him.

Records from his 2011 bankruptcy filing show Bowyer declared $425,000 in gambling losses at the Cosmopolitan and Aria casinos in Las Vegas between 2010 and 2011.

In 2015, Bowyer received a $1.2 million line of credit from the Foxwoods Resort Casino in Connecticut, which sued him three years later in tribal court to get the money back, according to court filings. As of last year, the Mashantucket Pequot Tribal Nation that owns the casino was still trying to recoup its funds.

ESPN’s Paula Lavigne and John Mastroberardino contributed to this report.

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‘Frustrated’ Scherzer scratched from rehab start

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'Frustrated' Scherzer scratched from rehab start

ARLINGTON, Texas — Texas Rangers right-hander Max Scherzer was scratched from his second scheduled rehab start Tuesday because of thumb soreness.

The soreness is similar to what Scherzer experienced last year before being sidelined for the end of the regular season and the start of the playoffs for the World Series champion Rangers.

Scherzer is rehabbing from surgery in mid-December to repair a herniated disk in his lower back, and he said that isn’t giving him any issues.

“I’m frustrated. You want to be out there pitching. I’ve put myself in a position to get back out there,” Scherzer said. “Coming off the back surgery, I’ve jumped through every hoop and really been putting myself in position to help the team out sooner than anybody thought. And the reason I’m not going out there is a thumb injury.”

Texas manager Bruce Bochy classified it as a “minor setback” for the three-time Cy Young Award winner.

“You’re talking days, not weeks,” Bochy said.

The 39-year-old Scherzer had been scheduled to start for Double-A Frisco at Corpus Christi on Tuesday night. That was six days after the eight-time All-Star threw 52 pitches into the third inning of his first rehab start for Triple-A Round Rock.

Scherzer said the inside ligament on his right thumb bothered him some in a simulated game before that, but he was able to manage in the start for Round Rock. Things changed in the past few days while preparing to start another game.

“Coming out of the bullpen, it was just going to get worse. And then it was starting to leak into the forearm. The forearm was starting to get tight on me,” Scherzer said. “Just need a couple days to let everything breathe, get everything back underneath me. There’s nothing really structurally wrong. It’s just some discomfort and just need to let it subside so nothing bad happens.”

The Rangers acquired Scherzer from the Mets in a deadline trade last July after the pitcher agreed to opt in on the final year of his contract for this season at $43.3 million. New York is paying $30.83 million of that to Texas in twice-monthly installments.

After the trade, Scherzer was 4-2 with a 3.20 ERA in eight starts for the Rangers, the last in the regular season Sept. 12 before being sidelined by a muscle strain in his shoulder. He returned to make two starts in the American League Championship Series, then Game 3 of the World Series before exiting after three innings because of his back.

Scherzer said Tuesday he had some thumb soreness in the regular season last year that became forearm tightness and led to the shoulder issue.

“That was the progression last year, and this was starting to mimic it,” Scherzer said.

As for the rehab of his back and how it was recovering, Scherzer said he had the kind of velocity he would have in spring training in the start for Round Rock. He said it was a normal ramp-up in an effort to get back into the Rangers’ rotation.

His 3,367 career strikeouts are the most among active pitchers, and he is second on the active list with 214 wins and 448 games started.

“We’ll let this thing clear up a little,” Bochy said. “You have to expect these things, especially when a guy’s coming back from a pretty good layoff. The good news is it’s not his back. His thumb’s a little sore, and that will clear up.”

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