What Would It Take to Make a MRSA Vaccine?

If you accept that MRSA, drug-resistant staph, kills up to 19,000 people per year in its most virulent forms, and causes at least 7 million primary-care and ER visits per year — and there’s no reason to doubt either of those estimates, which were published in the Journal of the American Medical Association and the Archives of Internal Medicine — then it’s reasonable to ask: Why can’t we prevent it?

I wrote a book on MRSA, immersing myself for several years in thousands of medical-journal articles and hundreds of patients’ stories, and when I surfaced from all that, I had the same question. Why don’t we have a vaccine against MRSA? How hard could it be?

The answer, as it turns out, is: surprisingly, heartbreakingly hard.

In the current issue of the international journal Nature, available in print and on the web today, I take a deep dive into the state of research into the possibility of a MRSA vaccine. Turns out, people have been trying for several decades now, but the wily, infinitely adaptable bacterium S. aureus — a bug that, thanks to its millennia of evolutionary history with us, bristles with defenses against our immune systems — has frustrated all attempts.

So far, anyway. The point of the story is to tell the tale of Dr. Robert Daum, who identified the first recognized cases of community-associated MRSA in the 1990s, and who thinks he has a new, even heretical idea, for a MRSA vaccine.

Over the past 10 years, as MRSA has become resistant even to last-resort antibiotics, several pharmaceutical companies have launched research programmes for vaccines, some with Daum’s input. But Daum contends that they underestimate the enemy by relying on the standard immunological approach of triggering the production of protective antibodies. Instead, he advocates a strategy that stimulates T cells, part of a different branch of the immune system. It is an ambitious proposal and not all infectious-disease specialists are convinced that it will work.

The idea that Daum and his team have, to base a vaccine on stimulating Th-17 lymphocytes and production of interleukin-17, is in such early stages that they are still doing basic science, and at least 5 years from even a Phase I formula. But it is one of the few truly new ideas in staph-vaccine immunology, and it is based on an early-phase vaccine that stimulated Th-17 in mice and has gone on to commercial development. The originator of that vaccine, Dr. Brad Spellberg, is now collaborating with Daum. (Constant readers may remember Spellberg as the author of Rising Plague, about antibiotic resistance and failures of drug development.)

Even if the Daum group’s hypothesis works, it probably won’t be enough; they may have to consider combining whatever formula they achieve with traditional antigen-antibody approaches, or other new ideas such as interfering with binding of antibodies by protein A. And that’s not even mentioning the hurdles that would lie in wait for any new vaccine in a society that is increasingly suspicious of them.

From his 20-plus years observing MRSA’s extraordinary rise — along with the crash in development of new drugs — Daum thinks it’s worth a try. “We can’t treat this,” he told me. “We have to prevent it. Vaccines prevent disease better than any anti-infectives ever could.”

I hope you’ll take a look.

Cite: McKenna M. Man vs. MRSA. Nature 482, 23–25 (02 February 2012) doi:10.1038/482023a