Sen. Bill Cassidy’s advocacy for vaccines and his résumé as a doctor have defined his political career.

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Now, those credentials are putting his Senate future in peril as Cassidy, R-La., prepares for the most difficult primary of his life Saturday.

Members of the “Make America Healthy Again” movement — a separate but overlapping wing of the MAGA movement that fully fused with President Donald Trump’s coalition in 2024 — have been working hard to take Cassidy down and install Trump-backed Rep. Julia Letlow as the Republican nominee for the Senate in deep-red Louisiana.

Cassidy was the key vote to confirm Robert F. Kennedy Jr., a longtime anti-vaccine activist, as health and human services secretary. But since then, Cassidy, a physician who is pro-vaccine, has found himself in conflict with Kennedy and his allies, including months of clashes with Kennedy over his vaccine skepticism and his actions at the Department of Health and Human Services.

And while Cassidy’s vote to convict Trump on Jan. 6-related impeachment charges in 2021 also made him a target of the right, it’s the tense relationship between Cassidy and Kennedy’s MAHA movement that has really boiled over ahead of the primary. Early this month, Trump blamed Cassidy — who chairs the Health, Education, Labor and Pensions Committee — for standing in the way of Dr. Casey Means’ nomination to be surgeon general, forcing Trump to replace her with a new nominee. Means is a wellness influencer and close ally of Kennedy.

“I nominated Casey, a strong MAHA Warrior, at the recommendation of Secretary Kennedy, who understands the MAHA Movement better than anyone, with perhaps the possible exception of ME!” Trump wrote on social media. “Nevertheless, despite Senator Cassidy’s intransigence and political games, Casey will continue to fight for MAHA on the many important Health issues facing our Country.”

Up until that social media post, Trump hadn’t directly attacked Cassidy much, despite having endorsed Letlow in January. But the Means saga clearly touched a nerve.

Kennedy also accused Cassidy of holding up the nomination and “sabotaging” Means’ appointment.

“Bill Cassidy once again did the dirty work for entrenched interests seeking to stall the MAHA movement and protect the very status quo that has made America the sickest nation on earth,” he wrote on X.

Leaving the Capitol that day, Cassidy told reporters that the White House had “known for a while [Means] didn’t have the votes to pass.” Despite Trump’s calling him a “very disloyal person,” Cassidy said he is “loyal to the United States of America” and argued he has delivered more for Louisianans than Letlow or his other primary opponent, state Treasurer John Fleming. If no candidate gets majority support Saturday, the top two finishers will head to a runoff.

It’s far from the only time that Cassidy’s perch atop the Senate health committee has brought him into conflict with Kennedy. Cassidy criticized Kennedy over his vaccine policy and abortion medications at a hearing last month, and he also debunked Kennedy’s interpretation of a scientific study. It was Kennedy’s first appearance before the committee in nearly a year, even though he had promised Cassidy he would appear once a quarter if asked. Cassidy requested that Kennedy testify back in September.

Asked how much he is hearing about MAHA issues from Louisiana voters, Cassidy told NBC News on Wednesday, “Not at all.”

For months, Kennedy ally Tony Lyons has been warning that if an incumbent Republican failed to align with the MAHA agenda, their political career could meet an “untimely demise.” In a February memo obtained by NBC News that was sent to congressional Republican leadership and fundraisers, Lyons shared new polling and argued that Republicans need to embrace the MAHA agenda or risk losing in the 2026 midterms.

How Letlow fares in the primary will be a test case for the MAHA movement as it tries to flex its muscles in the midterms. Lyons is supporting her Saturday, and he pledged $1 million through his MAHA PAC to help defeat Cassidy even before she entered the race. But two days before the primary, MAHA PAC has delivered on about half of that promise, pouring around $600,000 into ads, mailers and text campaigns supporting Letlow and opposing Cassidy, according to campaign finance filings.

Cassidy, meanwhile, has largely downplayed his differences with the MAHA movement. In an interview last month, he highlighted some of the areas in which they are aligned and argued that on the topic of vaccines, more voters may be on his side now that people have seen the deadly consequences of not getting vaccinated.

“MAHA and I are totally united on ultraprocessed foods, and we’ve had great success there,” Cassidy told NBC News. “Clearly, I have differences with some on immunizations, but I think when we see those thousands of people getting measles in these outbreaks and children dying from measles and other vaccine-preventable diseases, folks are kind of open to this. They understand that this is important.”

Letlow has embraced MAHA’s support and introduced a bill to codify Kennedy’s dietary guidelines and “promote healthier eating for Americans.” In the closing weeks of the campaign, she has focused much of her messaging on the MAHA movement.

“As a strong mama bear, I’m fiercely wanting to protect my two children, and I’ve met so many moms along the way on the trail who feel the exact same,” she said in an interview last month. “I’m so excited about the great work that Secretary Kennedy and the MAHA movement are doing when it comes to nutrition — nutrition choices for people across this country, for our children.”