By injecting each of the 19 target proteins into mice and measuring the immune response, they identified the four proteins that generated the strongest immune response. Two of those proteins, IsdA and IsdB, help the microbe acquire needed iron from the host's red blood cells. The other two, SdrD and SdrE, are thought to be involved in bacterial adhesion to host tissues.
When tested alone as a vaccine, each of the four proteins provided only partial or no protection. Fifty to 70 percent of mice vaccinated with one of these proteins and injected with a dose of a laboratory strain of the bacteria calculated to kill 50 percent of the mice, were still alive one week later.
When they vaccinated the mice using the combined vaccine, however, all of the mice survived. Although unvaccinated mice had clear evidence of kidney infections, the "bacterial load" in vaccinated mice was reduced "to a level below detection."
The next step was to test the vaccine's ability to protect mice from multiple bacterial strains isolated from humans. The researchers vaccinated 50 mice. Three weeks later, they injected groups of 10 with potentially lethal doses of one of five different clinical isolates.
The vaccine completely protected mice against two strains--including the virulent community-associated strain--and offered significant protection, resulting in 60- to 90-percent survival, against three other strains. All unprotected mice injected with the USA100 strain died within 36 hours, for example, but 60 percent of vaccinated mice survived injection with that strain.
"Further testing," said first author of the study Yukiko K. Stranger-Jones, a graduate student in the Schneewind
Source:University of Chicago Medical Center