Development of vaccines to CS2 protein on enterotoxigenic Escherichia coli.
This invention identifies the nucleotide sequence encoding a CS2 pilin protein of enterotoxigenic Escherichia coli. Also identified are the nucleotide sequences of coding sequences linked to the CS2 coding sequence, which other coding sequences must be expressed to allow the synthesis and assembly of the CS2 pili on the cell surface.
Enterotoxigenic Escherichia coli strains (ETEC) are a major cause of diarrheal disease. Accordingly, there is a need for a vaccine for preventing the diseases associated with these bacteria. Ideally, a vaccine generates a protective immune response in which it interferes with a very early step in the infectious process, for example, by preventing the attachment of the pathogenic bacterial cells to host tissue. In the case of ETEC, this attachment step is believed to be mediated by pili, which are long, proteinaceous structures extending out from the surface of the bacterial cells. The CS2 pili are believed to mediate attachment to and/or promote colonization of the human upper intestine.
There is a long felt need in the art for vaccines useful in protecting against diarrheal disease resulting from infection with ETEC, including CS2 ETEC. Because of the serological diversity in pili of ETEC, an ETEC vaccine advantageously includes antigenic determinants (epitopes) from more than one pilus type to be effective against more than one type of ETEC infection, or a single vaccine can include one or more conserved antigenic determinants.