Recombinant Salmonella is a highly versatile vectorcapable of delivering disease-causing antigens originating from viruses, bacteria and parasites. An attenuated Salmonella vaccine against pneumonia, developed in the Curtiss lab, is currently in FDA phase 1 clinical trials.
In the current research, the team describe a method aimed at retaining the immunogenicity of an anti-pneumonia RASV while reducing or eliminating unwanted side effects sometimes associated with such vaccines, including fever and intestinal distress. "Many of the symptoms associated with reactogenic Salmonella vaccines are consistent with known reactions to lipid A, the endotoxin component of the Salmonella lipopolysaccharide (LPS)," the the major surface membrane component , Kong explained. "In this paper, we describe a method for detoxifying the lipid A component of LPS in living cells without compromising the ability of the vaccine to stimulate a desirable immune response."
To achieve detoxification, Salmonella was induced to produce dephosphoylated lipid A, rendering the vaccine safer, while leaving its ability to generate a profound, system-wide immune response, intact.
To accomplish this, a recombinant strain of Salmonella was constructed using genes from another pathogen, Francisella tularensis, a bacterium associated with tularemia or rabbit fever. Salmonella expressing lipid A 1-phosphatase from tularensis (lpxE) showed less virulence in mice, yet acted to inoculate the mice against subsequent infection by wild-type Salmonella.
In further experiments, the group showed that Salmon
|Contact: Joseph Caspermeyer|
Arizona State University