title: Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells.
abstract: PspA is one of the most well studied pneumococcal proteins and a promising candidate for a future protein-based anti-pneumococcal vaccine. Nevertheless, its structural and serological variability suggests the inclusion of more than one PspA molecule in order to broaden protection. Since different PspAs exhibit variable levels of cross-reactivity, the selection of the protein combination with the highest coverage potential is an essential step for PspA-based vaccine development. This work investigated the level of cross-reactivity within family 1 PspAs, and established a complement based antibody mediated opsonophagocytic assay for measuring the level of cross-protection. Among a panel of ten family 1 PspA molecules, two of them, one belonging to clade 1 and another from clade 2, induced antibodies capable of enhancing complement deposition and mediating the phagocytic killing by mouse peritoneal macrophages of all pneumococci bearing PspA family 1 strains tested, regardless of their serotype. Therefore, we suggest the inclusion of either one in a PspA-based vaccine, as a representative of family 1. Furthermore, our results suggest that opsonophagocytosis by mouse peritoneal cells can be an efficient means of evaluating the induction of protective immune responses in mice across a large number of strains.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Cibelly
authors.initials: C
authors.lastname: Goulart
authors.forename: Michelle
authors.initials: M
authors.lastname: Darrieux
authors.forename: Dunia
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Fabiana C
authors.initials: FC
authors.lastname: Pimenta
authors.forename: Maria Cristina C
authors.initials: MC
authors.lastname: Brandileone
authors.forename: Ana Lucia S S
authors.initials: AL
authors.lastname: de Andrade
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; C051592:pneumococcal surface protein A; D003165:Complement System Proteins