title: Identification of a Monoclonal Antibody Against Pneumococcal Pilus 1 Ancillary Protein Impairing Bacterial Adhesion to Human Epithelial Cells.
abstract: The adhesion of Streptococcus pneumoniae is a key step during colonization of human respiratory tract mucosae. Here we demonstrate that pneumococcal type I pilus significantly increases the adhesiveness of poorly adhering highly capsulated strains in vitro. Interestingly, preincubation of bacteria with antibodies against the major pilus backbone subunit (RrgB) or the adhesin component (RrgA) impaired pneumococcal association to human epithelial cells. Screening for anti-RrgA monoclonal antibodies specifically affecting the adhesive capacity of S. pneumoniae led to the identification of the monoclonal 11B9/61 antibody, which greatly reduced pilus-dependent cell contact. Proteomic-based epitope mapping of 11B9/61 monoclonal antibody revealed a well-exposed epitope on the D2 domain of RrgA as the target of this functional antibody. The data presented here confirm the importance of pilus I for S. pneumoniae pathogenesis and the potential use of antipilus antibodies to prevent bacterial colonization.
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Amerighi
authors.affiliation: Institute for Immunology, University of California-Irvine School of Medicine.
authors.forename: Maria
authors.initials: M
authors.lastname: Valeri
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Danilo
authors.initials: D
authors.lastname: Donnarumma
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maccari
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Monica
authors.initials: M
authors.lastname: Moschioni
authors.affiliation: Interdepartmental Centre for Electron Microscopy, University of Tuscia, Viterbo, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Taddei
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lapazio
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Werner
authors.initials: W
authors.lastname: Pansegrau
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Scilla
authors.initials: S
authors.lastname: Buccato
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Gabriella
authors.initials: G
authors.lastname: De Angelis
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggiero
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Vega
authors.initials: V
authors.lastname: Masignani
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Marco
authors.initials: M
authors.lastname: Soriani
authors.affiliation: GSK Vaccines, Siena.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pezzicoli
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D018604:Epitope Mapping; D036781:Fimbriae Proteins / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000276:immunology*; D006801:Humans; D013296:Streptococcus pneumoniae / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D037521:Virulence Factors; D036781:Fimbriae Proteins
keywords: RrgA; RrgB; Streptococcus pneumoniae; capsule; colonization; monoclonal antibodies; type 1 pilus; vaccines