Researchers have had another setback in their efforts to develop a vaccine… (Science Photo Library /…)
Staph infections remain a significant problem for hospital patients, and scientists are trying to develop vaccines to prevent Staphylococcus aureus bacteria from establishing itself in vital areas like the heart, lungs or blood. But it’s turning out to be a difficult task: A promising vaccine intended to protect heart-surgery patients from staph infections worked no better than a placebo, a new study reported.
Making matters worse, patients who developed staph infections despite getting the vaccine were more likely to die than infected patients who got the placebo, the study found.
The results, released Tuesday by the Journal of the American Medical Assn., were from a double-blind, randomized, placebo-controlled trial involving about 8,000 patients in 26 countries. The vaccine, dubbed V710, had seemed to work well in animals. In human volunteers, a single dose produced antibodies, as intended.
But the larger clinical trial was halted ahead of schedule, after safety monitors noticed that the vaccine (administered as a shot in the deltoid muscle or the thigh) didn’t protect patients better than the dummy shot when given under real-world conditions. The data also suggested that receipt of the vaccine was associated with a greater risk of multiorgan failure and death.
In the JAMA report, the international research team said that staph infections occurred at a rate of 2.6 cases per 100 person-years among patients who took the vaccine and 3.2 cases per 100 person-years among patients who took the placebo. That difference wasn’t large enough to be statistically significant.
V710 seemed to do a better job of preventing staph infections that could be treated with the antibiotic methicillin than in preventing the infections that were resistant to the drug. Methicillin-resistant Staphylococcus aureus, or MRSA, has become a major public health concern.
Multiorgan failure was more common in patients who got the vaccine than in patients who got the placebo; all of the patients who developed multiorgan failure died. But the data do not prove that the vaccine was responsible for the increased risk of staph infections or multiorgan failure observed in the heart surgery patients, the study authors noted.
These results came in spite of the fact that the vaccine “induced a significant, albeit modest and transient, increase in functional antibodies,” according to the JAMA report.
This isn’t the first time that a vaccine looked good in early tests but fell apart in later clinical trials. The study in heart surgery patients pointed out that the same thing happened with a staph vaccine that was tested in kidney patients on hemodialysis.
“The paradoxical finding of worse outcomes after receipt of a vaccine has been previously encountered,” the study authors wrote.
In an editorial that accompanies the study, Dr. Preeti Malani of the University of Michigan Health System wrote that a staph vaccine “would transform the infection prevention landscape.” But the goal is likely to remain elusive. “This study of V710 joins a long list of unsuccessful trials” aimed at preventing staph, he wrote. “Fittingly, some have described the development of staphylococcal vaccines as dreaming the impossible dream.”
The most important lesson to draw from this latest clinical trial is that researchers must find ways to fight -- and even better, to prevent -- dangerous bacterial infections in the first place, Malani wrote.
“Burgeoning antimicrobial resistance results in an urgent, worldwide public health mandate,” he wrote. “Despite significant disease burden, National Institutes of Health funding for healthcare-associated infections is not proportionate to the burden of disease.”