Researchers step closer to E. coli vaccine

Transmission electron micrograph of E. coli O157:H7 showing flagella. CDC/Peggy S. Hayes. Photo by Elizabeth H. White, M.S.Although Escherichia coli (E. coli) commonly colonizes the human digestive tract and most of its infections are benign, some strains of the bacteria can be quite dangerous. A major subgroup of E. coli, called “extraintestinal pathogenic E. coli” (ExPEC) includes strains that are responsible for more than 80% of urinary tract infections, and are the second-leading cause of neonatal meningitis and sepsis cases (blood poisoning). Urinary tract infections are associated with high health care costs, and sepsis with high infant mortality rates; in addition, the ExPEC strains have shown increasing resistance to antibiotics. In light of these issues, the development of an effective vaccine has become an important priority in combating ExPEC strains.

Now, researchers have used “reverse vaccinology” techniques to identify specific proteins in a particular ExPEC strain–proteins that could possibly provoke an immune response and be used to create a vaccine.

A reverse vaccinology approach consists of examining a pathogen’s genome to find genes with attributes that could make good targets for vaccines. The researchers in this E. coli study examined the genome sequence of ExPEC IHE3034, an E. coli strain isolated from a case of neonatal meningitis.

They compared the IHE3034 sequence with that of other E. coli strains, both from the ExPEC subgroup as well as from nonpathogenic strains (those that can’t cause illness). Using reverse vaccinology, they identified 230 proteins that were present in ExPEC, but missing or present with only low similarity in nonpathogenic strains, and which might be protective against bacterial infection.

The researchers administered the proteins to mice, then “challenged” the mice with a lethal dose of pathogenic E. coli. (“Challenging” in this case means attempting to infect a subject after providing them with some form of protection against the pathogen.) They found nine of the proteins to be potential vaccine candidates, with a protection efficacy ranging from 13% to as high as 82%. In addition, they found that some of the nine proteins were also present in non-ExPEC pathogenic strains, raising the possibility that a vaccine created using one or more of these proteins could be broadly protective against strains of E. coli that cause illness, not just those from the ExPEC subgroup.

Identification of protective and broadly conserved vaccine antigens from the genome of extraintestinal pathogenic Escherichia coli
Danilo Gomes Moriel, Isabella Bertoldi, Angela Spagnulo, Sara Marchi, Roberto Rosini, Barbara Nesta, Ilaria Pastorello, Vanja Mariani Corea, Giulia Torricelli, Elena Cartocci, Silvana Savino, Maria Scarselli, Ulrich Dobrindt, Jorg Hacker, Herve Tettelin, Lothar Wieler, Christa Ewers, Derek Pickard, Gordon Dougan, Maria Rita Fontana, Rino Rappuoli, MariaGrazia Pizza, and Laura Serino
Proceedings of the National Academy of Sciences DOI 10.1073/pnas.0915077107
Link to article: http://www.pnas.org/cgi/doi/10.1073/pnas.0915077107