Researchers at the Arizona State University's Biodesign Institute are hoping that infant bacterial pneumonia could soon be treated with two vaccine candidates that they've developed.
Research leader Roy Curtiss, an investigator of vaccines and infectious diseases, has revealed that the two vaccine strains draw on the properties of an unlikely vaccine carrier-one generally associated with causing sickness rather than safeguarding the body against it.
Salmonella typhimurium, a rod-shaped motile pathogen, is one of over 2000 strains or serotypes of the Salmonella constellation of bacteria, which are responsible for causing serious and oft-fatal diseases to which children under two years of age are particularly vulnerable.
Due to this fact, Salmonella's choice as the principal component in a new vaccine for babies has been something of a hard sell.
"People said 'you gotta be kidding,'" says Curtiss, noting that twenty years ago, Salmonella outbreaks were a grave concern in nurseries and hospitals, sometimes leading to the deaths of over half the children in such facilities.
Now, Curtiss and lead author Yuhua Li have led the development of two new vaccine candidates, labeled x9088 and x9558, under grants from the NIH and the Bill and Melinda Gates Foundation.
The researchers say that the novel strains belong to a family known as recombinant attenuated Salmonella vaccines (RASVs). They say that the critical component boosting their effectiveness is a delayed mechanism of attenuation.
According to them, Salmonella's notorious virulence is essentially short-circuited, but only after it has stimulated a robust systemic immune response to pneumococcal surface protein A (PspA), a vital bacterial pneumonia antigen.
The researchers say that this feat is achieved by using genetic trickery to tame S. typhimurium, producing altered bacterial strains requiring mannose and/or arabinose-sugars available in the lab, but absent in the human body.
After roughly seven cell divisions, the bacterium exhausts its stores of specialized sugar. Unable to sustain the integrity of its cell wall, it bursts.
This approach can help place Salmonella on a self-destruct timer, one that may be sensitively tuned to achieve maximum immunogenicity following colonization of host tissues.
Describing the technique in PNAS, the researchers revealed that an initial version of the new vaccine is soon to begin the first pre-clinical trials in human subjects.