After several vaccines were proven to be effective in animals, they subsequently failed in human trials. But now this decades-long conundrum has finally been solved.

Staphylococcus aureus is a bacterium that occurs in many people, especially on the skin and in the nose. In general, the bacteria is harmless. Occasionally, however, the otherwise harmless bacteria turns into a pathogen, causing various skin infections or even food poisoning. For more than a century, scientists have been searching for an effective vaccine, but without much success. And now scientists think they finally know why.

Puzzle

Researchers have been baffled for decades. The search for a vaccine against staphylococci always seems to be a dead end. At least fifteen successful preclinical animal studies have been conducted over the past thirty years, proving the effectiveness of proposed vaccines. But in all subsequent human trials, these vaccines failed. “It’s a long-standing and one of the most puzzling problems facing staphylococci,” said study researcher George Liu. “None of these human trials succeeded. And scientists just don’t understand why.”

Urgent

However, the need for an effective vaccine is becoming increasingly urgent. This is mainly due to the spread of the methicillin-resistant Staphylococcus aureus (MRSA). Also known as the ‘hospital bacteria’, this bacteria has become resistant to many antibiotics commonly used to treat staphylococci. The bacterium mainly causes infections and epidemics in hospitals and healthcare institutions. And a recently published study found that bacterial antimicrobial resistance led to tens of millions of infections and 1.2 million deaths worldwide in 2019, with MRSA as the leading cause. “Vaccines are therefore the most effective way to reduce the health burden and tackle antibiotic resistance,” concludes Liu.

Declaration

In a new study, Liu and his colleagues set out to find the answer to the most pressing question: how come a vaccine against staphylococci has failed? The researchers hypothesized that it could possibly be related to previous exposure to the bacteria. “Laboratory mice rarely come into contact with S. aureussaid researcher Chih-Ming Tsai. “But people are exposed to staphylococci from the first weeks of life.” In fact, within two months, half of the babies have active colonies and abundant antibodies. “We therefore suspect that if mice are also infected before vaccination, the proposed vaccines may also not work in them,” Tsai said.

Experiments

To test this hypothesis, the researchers conducted a series of experiments with the IsdB vaccine; a vaccine that has been developed to combat staphylococci, but has not been shown to work in humans. And indeed, the vaccine worked in the mice that had not been exposed to staphylococci. But when the researchers vaccinated mice that had previously come into contact with the bacteria, the vaccine did nothing. The researchers also discovered why. It seems that S. aureus developed strong defense mechanisms. “The bacterium has devised a strategy to render our immune response against them ineffective,” explains Tsai.

Declaration

According to the researchers, this explains a lot. Thus, they say, it shows why in the past all human trials of proposed vaccines against staphylococci have failed. “It’s even possible that the same principle explains why trials with many other vaccines have failed,” Tsai says.

They are promising findings. Because now that researchers better understand why previous vaccine trials failed, they can also effectively look for ways to deal with the problems. The researchers already have an idea how. For example, they managed to use the newly acquired knowledge to develop a vaccine that was also successful in mice that had previously been exposed to S. aureus† “If our results are confirmed, an effective vaccine against staphylococci may not be far away,” concludes Tsai.