An antibody to beat staph at its own game

Staphylococcus aureus

Staphylococcus aureus

About 60,000 infants are born prematurely each year with very low birth weight—less than 1,500 grams (3 pounds, 5 ounces)—requiring hospitalization and intensive care. A 2012 study showed that 3.6 percent of these babies develop sepsis or meningitis from Staphylococcus aureus infections, with a 26 percent rate of mortality and often leading to severe neurological issues for those who survive.

These babies are at high risk for developing staph infections because their immune systems aren’t fully developed; they hadn’t yet received a full complement of antibodies from their mothers. S. aureus is a particularly elusive pathogen too. Since it can cause infection in any part of the body, it has evolved an elaborate toolset to defend itself against the immune system. Some methicillin-resistant, or MRSA, strains now even resist workhorse antibiotics like penicillin.

In a study recently published in the journal Vaccine, University of Chicago microbiologist Olaf Schneewind, MD, PhD, and his team showed how to beat S. aureus by taking away one of its primary tools. The findings mean that someday physicians could have a new antibody at their disposal to protect very low birth weight infants from staph infections, and prevent recurring infections in other at-risk patients.

Olaf Schneewind, MD, PhD

One of the weapons S. aureus uses to evade the immune system is a protein called staphylococcal protein A (SpA). Normally, when the body’s immune system detects an antigen (a virus or bacteria like S. aureus), it produces antibodies that can neutralize it before it does anything bad. But SpA turns the tables and neutralizes the antibodies first.

“Protein A is an interesting molecule,” Schneewind said. “It binds to the antibodies and neutralizes their effective function. So the argument is that if you have an antibody against S. aureus that cannot be neutralized by Protein A, then not only will you neutralize this surface attribute of the organism [SpA], but you also provide an antibody for the antigen itself.”

Schneewind and his team were able to isolate antibodies from mice and rabbits that did just that—neutralize the SpA protein produced by S. aureus before it could short-circuit the immune response. When newborn mice pups in this study were given the SpA-neutralizing antibody, they were protected against infections.

This antibody has a second potential use in boosting the immune system’s adaptive immune response against future infections. Normally the body’s B cells, tiny factories that produce antibodies, recognize antigens and produce more B cells and antibodies to fight back. The immune system tries to do this against S. aureus, but normally its SpA dampens the response.

In Schneewind’s experiment however, mice that were able to fight off staph infections with the new antibody were immune to subsequent infections too. This could potentially help protect patients who are at risk for recurring skin infections from staph, such as diabetics who develop foot ulcers.

Schneewind and his team have created a version of this antibody that can be given to humans, and look forward to starting clinical trials to test its safety and effectiveness. The potential payoff, he says, is worth it.

“The cost in human life, and the cost in medical care that’s associated with infections in these very low birth weight infants is terrifying, just mind boggling,” Schneewind said. “We owe it to ourselves to try.”

About Matt Wood (531 Articles)
Matt Wood is a senior science writer and manager of communications at the University of Chicago Medicine & Biological Sciences Division.
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