Selection of Family 1 PspA Molecules Capable of Inducing Broad-Ranging Cross-Reactivity by Complement Deposition and Opsonophagocytosis by Murine Peritoneal Cells

Vaccine. 2011 Feb 11;29(8):1634-42. doi: 10.1016/j.vaccine.2010.12.074. Epub 2011 Jan 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology*
  • Complement System Proteins / immunology*
  • Cross Protection*
  • Cross Reactions / immunology
  • Female
  • Macrophages, Peritoneal / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Phagocytosis*
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / immunology
  • Streptococcus pneumoniae / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Pneumococcal Vaccines
  • pneumococcal surface protein A
  • Complement System Proteins