Drug-resistant bacteria are making public health officials nervous, and a team of scientists from Brigham and Women’s Hospital think they may have two possible solutions to the problem: vaccines and antibodies designed to take on not just one superbug, but many of them.
By cutting off superbugs at the pass, these alternatives to antibiotics could save millions of people in the coming years.
Vaccines contain little bits of viruses and bacteria, or things that look like these invaders, that prime your immune system’s defence system, including your own antibodies, to fight off an invader before you get sick. They have worked for everything from chickenpox to rubella.
Antibodies in the form of a drug, on the other hand, work in a similar way, except instead of waiting for your body to produce them naturally, they can work immediately after injection.
Now researchers think they have found a way to use these two experimental interventions to target a key protein that sits outside of many antibiotic-resistant bacteria, effectively destroying the bacteria directly with the antibody or kickstarting your body’s natural production of the antibody with the vaccine.
An impending crisis
Antibiotic-resistant bacteria are a big problem. They don’t respond to any of the drugs we currently have, and are even stronger and deadlier than we thought.
Not only are our current drugs not working, but over the past 20 years, the number of new antibiotics approved by US Food and Drug Administration (FDA) has been steadily declining. Many of the large pharmaceutical companies, such as Pfizer, have stopped working on these drugs altogether. Right now there are 40 new antibiotics in development, compared to 771 new therapeutics and vaccines for cancer that are in clinical trials or awaiting approval.
As a result, public health officials are racing to implement measures to decrease rates of antibiotic resistance worldwide by curtailing prescription rates, removing them from animal feed, and eliminating the need for the drugs in the first place by promoting good hygiene.
But even together, these approaches are not enough.
“Just focusing on antibiotics is not the best idea,” researcher David Skurnik, assistant professor of medicine at Brigham and Women’s Hospital, told Tech Insider. “Antibiotic resistance emerges so fast, and it’s a cycle that we don’t want to keep going. We need an alternative approach.”
A novel approach
Skurnik thinks he’s found a promising alternative to address the waning power of antibiotics. In the early 2000s, scientists discovered that many deadly, multi-drug-resistant bacteria express a specific molecule on the surface of their cells called poly-β-(1-6)-N-acetylglucosamine — or more simply, PNAG.
PNAG is like an identification tag for bad bacteria. Your own antibodies can recognise this molecule and then mark it for destruction by the body’s white blood cells, hopefully stopping the bacteria before it kills.
Scientists have already identified the specific human antibody that our bodies produce naturally and bind to PNAG — called MAb F598. Our own supply of MAb F598 usually isn’t enough to kill the bad bacteria on its own, so Skurnik’s team’s plan is to grow and deliver a stronger form of MAb F598 directly into the body in the form of a drug.
Preliminary experiments in mice suggested that this antibody successfully treated Staphylococcus aureus infections without toxic effects, something that’s an important step but is true of many treatments that never make it to market. Skurnik and co-investigator Gerald Pier, professor of medicine at Harvard Medical School, took it one step further and tested the safety and efficacy of the antibody as a drug in a small group of humans in the summer of 2010. As with the mice, the drug appeared to be safe and effective against Staphylococcus aureus infections, though the sample size was small.
The team is currently preparing to test the antibody’s effectiveness and safety in larger groups of people in phase II clinical trials, which are slated to begin in early 2016, Pier told Tech Insider.
There’s still a long road ahead for the drug. While about 70% of new drugs pass phase I clinical trials, only about a third pass both phase I and II clinical trials before continuing on to phase III, where the drug might still fail or be found dangerous. That’s also when the FDA can approve it for commercial sale. A drug then continues on to phase IV, where pharmaceutical companies monitor a drug’s long-term safety and effectiveness.
In addition to the antibody, the team is also in the process of developing a synthetic vaccine that primes your body to make more of the MAb F598 antibody to attack PNAG before you get sick. They haven’t yet tested the vaccine in humans. A vaccine would take longer than a shot of antibodies to become effective, but generally could have longer lasting effects and can stop you from getting sick in the first place.
Pier and Skurnik’s team has already begun testing the vaccine for safety and toxicity in miniature pigs. They expect to file an Investigational New Drug application with the FDA at the end of 2015 or early 2016, and they hope to begin phase I clinical trials in early 2016, Pier said.
If the trials pan out successfully — something that’s by no means a sure thing at this point — both the vaccine and the antibody could protect against a broad spread of deadly drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, or MRSA, which has spread widely since its first appearance in 1960 and currently kills about 11,000 people in the US each year. It might also be effective against carbapenemase-producing Enterobacteriaceae — a class of bacteria resistant to nearly all “last resort” antibiotics.
We currently have vaccines or antibodies for the bacteria that cause pneumonia, meningitis, and certain stomach bugs, but each drug only targets that specific bug. Others, designed to fight MRSA in particular, have been in development for decades.
The anti-PNAG vaccine and antibody, if successful, would protect or fight against a broad variety of the most frequent and deadly antibiotic-resistant bacteria all in one — a first. But we are still many years away from knowing how successful this could be.
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