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Why Don’t Staph Vaccines Work Well For Humans

Staphylococcus aureus, the bacteria that causes the common staph infection, usually poses no risk for humans. The human gut boasts millions of different bacteria — some good, some bad, some indifferent — though on rare occasions a benign strain can become an opportunistic pathogen.

Interestingly enough, scientists cannot develop a reliable vaccine for the staph infection despite dozens of clinical trials.

“It’s a longstanding, and one of the most enigmatic, issues of the staphylococcal field,” said George Liu, MD, Ph.D., 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.”

And because strains of bacteria continue to evolve and learn to outperform antibiotics, certain types of staph, like methicillin-resistant S. aureus (MRSA), has become essentially untreatable. Now, MRSA is the primary source of infections acquired within hospitals and other health care settings, such as nursing homes. A recent study estimated that bacterial antimicrobial resistance resulted tens of millions of infections and 1.2 million deaths worldwide in 2019, with MRSA as the primary culprit.

“Vaccines are the most effective way to cut down that health burden and reduce antibiotic resistance,” said Liu.

The staph infection conundrum effectively boils down to a protective component of a protein that bacteria use to acquire iron

Senior author Liu and colleagues think they may have discovered an answer to the mystery of Staphylococcus aureus. The answer lies, ironically, in the original question: why is a relatively common infection so hard to isolate and defend against? The writers of the study believe vaccine trials have not worked because the mice that researchers use for testing are bred to be blank slates, which makes sense given that you want to eliminate variables in scientific research. But in the case of staph, the blank slate is misleading, because the rodents never had a chance to develop a “real world” version of staph that has mutated and changed a bit like a typical human being’s staph.

You see, staph is so common that it looks slightly different in everyone, which is why a vaccine is difficult to develop. Mice respond extremely well to vaccines because the type of staph that doctors eventually add to the experiment is controlled and predictable; the same can’t be said for human staph.

“Staph vaccines appear so easy to make in laboratory mice because they rarely see S. aureus, but humans are exposed to staph beginning in the first weeks of life and, in order to coexist, staph appears to have developed many strategies to render ineffective our immune response against them,” first author Chih-Ming Tsai, Ph.D., said. “If mice had staph infections before vaccination, we think that the vaccine candidates might not work.”

In combination with other experiments, Liu said their findings indicate that faulty memory of a pathogen and its corresponding immune response likely lead to failed vaccine trials.

“It is even possible that the same principle might also explain why many other hard-to-make vaccines have failed,” he said. “If we are proven correct, an effective staph vaccine may not be too far away.”

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