Minor pilins as novel vaccine candidates against Neisseria meningitidis
Dr Ana Cehovin, Dr Vladimir Pelicic
- Start Date:
01 January 2008
Imperial College, London, UK
Besides the polysaccharide capsule, on which all the currently available vaccines are based, type IV pili (Tfp) are the only known surface-exposed structures present on all virulent meningococcal strains. These hair-like appendages, mainly composed of hundreds of copies of a single protein, the pilin, extend from the surface of a wide variety of bacterial pathogens in which they mediate several properties crucial for pathogenesis. The possibility to use Tfp or pilin subunits as vaccine candidates has long been recognized and tested in several human and animal pathogens. However, the extreme antigenic variability of pilin in Neisseria species, which occurs even during the course of an infection, has undermined the development of pilus-based vaccines. This project takes advantage of our recent finding that PilX is a minor pilin that assembles within Tfp in a similar way to pilin and modulates one of the Tfp-linked phenotypes, ie. bacterial aggregation. Unlike pilin, PilX is extremely conserved at the sequence level and could therefore be a suitable vaccine candidate for the development of a pilus-based vaccine offering broad protection against N. meningitidis infections. The aim of this project is to determine whether PilX, and the other likely minor components of meningococcal pili ComP and PilV, could represent novel antigens for inclusion in a vaccine providing universal protection against N. meningitidis.