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.”

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.

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

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California’s Office of Health Care Affordability faces a herculean task in its plan to slow runaway health care spending.

The goal of the agency, established in 2022, is to make care more affordable and accessible while improving health outcomes, especially for the most disadvantaged state residents. That will require a sustained wrestling match with a sprawling, often dysfunctional health system and powerful industry players who have lots of experience fighting one another and the state.

Can the new agency get insurers, hospitals, and medical groups to collaborate on containing costs even as they jockey for position in the state’s $405 billion health care economy? Can the system be transformed so that financial rewards are tied more to providing quality care than to charging, often exorbitantly, for a seemingly limitless number of services and procedures?

The jury is out, and it could be for many years.

California is the ninth state — after Connecticut, Delaware, Massachusetts, Nevada, New Jersey, Oregon, Rhode Island, and Washington — to set annual health spending targets.

Massachusetts, which started annual spending targets in 2013, was the first state to do so. It’s the only one old enough to have a substantial pre-pandemic track record, and its results are mixed: The annual health spending increases were below the target in three of the first five years and dropped beneath the national average. But more recently, health spending has greatly increased.

In 2022, growth in health care expenditures exceeded Massachusetts’ target by a wide margin. The Health Policy Commission, the state agency established to oversee the spending control efforts, warned that “there are many alarming trends which, if unaddressed, will result in a health care system that is unaffordable.”

Neighboring Rhode Island, despite a preexisting policy of limiting hospital price increases, exceeded its overall health care spending growth target in 2019, the year it took effect. In 2020 and 2021, spending was largely skewed by the pandemic. In 2022, the spending increase came in at half the state’s target rate. Connecticut and Delaware, by contrast, both overshot their 2022 targets.

It’s all a work in progress, and California’s agency will, to some extent, be playing it by ear in the face of state policies and demographic realities that require more spending on health care.

And it will inevitably face pushback from the industry as it confronts unreasonably high prices, unnecessary medical treatments, overuse of high-cost care, administrative waste, and the inflationary concentration of a growing number of hospitals in a small number of hands.

“If you’re telling an industry we need to slow down spending growth, you’re telling them we need to slow down your revenue growth,” says Michael Bailit, president of Bailit Health, a Massachusetts-based consulting group, who has consulted for various states, including California. “And maybe that’s going to be heard as ‘we have to restrain your margins.’ These are very difficult conversations.”

Some of California’s most significant health care sectors have voiced disagreement with the fledgling affordability agency, even as they avoid overtly opposing its goals.

In April, when the affordability office was considering an annual per capita spending growth target of 3%, the California Hospital Association sent it a letter saying hospitals “stand ready to work with” the agency. But the proposed number was far too low, the association argued, because it failed to account for California’s aging population, new investments in Medi-Cal, and other cost pressures.

The hospital group suggested a spending increase target averaging 5.3% over five years, 2025-29. That’s slightly higher than the 5.2% average annual increase in per capita health spending over the five years from 2015 to 2020.

Five days after the hospital association sent its letter, the affordability board approved a slightly less aggressive target that starts at 3.5% in 2025 and drops to 3% by 2029. Carmela Coyle, the association’s chief executive, said in a statement that the board’s decision still failed to account for an aging population, the growing need for mental health and addiction treatment, and a labor shortage.

The California Medical Association, which represents the state’s doctors, expressed similar concerns. The new phased-in target, it said, was “less unreasonable” than the original plan, but the group would “continue to advocate against an artificially low spending target that will have real-life negative impacts on patient access and quality of care.”

But let’s give the state some credit here. The mission on which it is embarking is very ambitious, and it’s hard to argue with the motivation behind it: to interject some financial reason and provide relief for millions of Californians who forgo needed medical care or nix other important household expenses to afford it.

Sushmita Morris, a 38-year-old Pasadena resident, was shocked by a bill she received for an outpatient procedure last July at the University of Southern California’s Keck Hospital, following a miscarriage. The procedure lasted all of 30 minutes, Morris says, and when she received a bill from the doctor for slightly over $700, she paid it. But then a bill from the hospital arrived, totaling nearly $9,000, and her share was over $4,600.

Morris called the Keck billing office multiple times asking for an itemization of the charges but got nowhere. “I got a robotic answer, ‘You have a high-deductible plan,’” she says. “But I should still receive a bill within reason for what was done.” She has refused to pay that bill and expects to hear soon from a collection agency.

The road to more affordable health care will be long and chock-full of big challenges and unforeseen events that could alter the landscape and require considerable flexibility.

Some flexibility is built in. For one thing, the state cap on spending increases may not apply to health care institutions, industry segments, or geographic regions that can show their circumstances justify higher spending — for example, older, sicker patients or sharp increases in the cost of labor.

For those that exceed the limit without such justification, the first step will be a performance improvement plan. If that doesn’t work, at some point — yet to be determined — the affordability office can levy financial penalties up to the full amount by which an organization exceeds the target. But that is unlikely to happen until at least 2030, given the time lag of data collection, followed by conversations with those who exceed the target, and potential improvement plans.

In California, officials, consumer advocates, and health care experts say engagement among all the players, informed by robust and institution-specific data on cost trends, will yield greater transparency and, ultimately, accountability.

Richard Kronick, a public health professor at the University of California-San Diego and a member of the affordability board, notes there is scant public data about cost trends at specific health care institutions. However, “we will know that in the future,” he says, “and I think that knowing it and having that information in the public will put some pressure on those organizations.”

This article was produced by KFF Health News, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

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KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

Subscribe to KFF Health News’ free Morning Briefing.