Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells |
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Authors: | Goulart Cibelly Darrieux Michelle Rodriguez Dunia Pimenta Fabiana C Brandileone Maria Cristina C de Andrade Ana Lucia S S Leite Luciana C C |
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Institution: | a Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil b Programa de Pós-Graduação Interunidades em Biotecnologia - USP - IPT - IB, São Paulo, Brazil c Laboratório de Biologia Molecular de Microrganismos, Universidade São Francisco, Av São Francisco de Assis, 218, 12916-900, Bragança Paulista, São Paulo, Brazil d Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA e Laboratório de Bacteriologia, Instituto Adolfo Lutz, São Paulo, Brazil f Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil |
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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. |
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Keywords: | Streptococcus pneumoniae Complement PspA Opsonophagocytosis |
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