Familiarity breeds exempt: Why staph vaccines dont work in humans: The sometimes-pathogenic bacteria has a long and intimate relationship with people, one that helps it fend off our immune response

For the most part, the bacterium Staphylococcus aureus is common and harmless, posing no threat to humans with whom they coexist. Occasionally, though, it can become an opportunistic pathogen, causing skin and bloodstream infections or food poisoning.

For more than a century, scientists have searched for an effective vaccine, including at least 15 successful preclinical studies using animal models in the past 30 years. In all of the subsequent human trials, however, these vaccine candidates failed.

“It’s a longstanding and one of the most enigmatic issues of the staphylococcal field,” said George Liu, MD, PhD, professor of pediatrics at University of California San Diego School of Medicine and chief of the Division of Infectious Diseases at Rady Children’s Hospital-San Diego. “None of these human trials have worked and scientists have struggled to find a reason.”

The question has gained greater urgency with the spread of methicillin-resistant S. aureus (MRSA), a type of staph bacteria that has become increasingly resistant to antibiotics commonly used to treat ordinary staph infections. MRSA is the primary source of infections acquired within hospitals and other health care settings, such as nursing homes. A study published in 2022 estimated that bacterial antimicrobial resistance resulted tens of millions of infections and 1.2 million deaths worldwide in 2019, with MRSA as the primary driver.

“Vaccines are the most effective way to cut down that health burden and reduce antibiotic resistance,” said Liu, pointing to successes with childhood inoculations and the more recent COVID-19 vaccines.

In a new paper, publishing July 7, 2022 in the journal Cell Host & Microbe, senior author Liu and colleagues say they may have found the answer to the conundrum of S. aureus, including the mechanism that explains why vaccine trials have so far failed and ways to overcome that.

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