2xtl

Publication Abstract from PubMed

Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin subunits from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens.

From the Cover: Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections.,Nuccitelli A, Cozzi R, Gourlay LJ, Donnarumma D, Necchi F, Norais N, Telford JL, Rappuoli R, Bolognesi M, Maione D, Grandi G, Rinaudo CD Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10278-83. Epub 2011 May 18. PMID:21593422^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.