Immunization with the RrgB321 fusion protein protects mice against both high and low pilus-expressing Streptococcus pneumoniae populations
| Autor: | Carole Harfouche, Vega Masignani, Paolo Ruggiero, Gabriella De Angelis, Esmeralda Bizzarri, Francesco Doro, Giuseppe Mancuso, Monica Moschioni, Michèle A. Barocchi, Elena Mori, Sara Filippini |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Recombinant Fusion Proteins
Population Biology medicine.disease_cause Pilus Pneumococcal Infections Microbiology Pneumococcal Vaccines Mice Phagocytosis In vivo Cell Line Tumor Streptococcus pneumoniae medicine Animals Humans education education.field_of_study Mice Inbred BALB C General Veterinary General Immunology and Microbiology Immune Sera Public Health Environmental and Occupational Health Gene Expression Regulation Bacterial biochemical phenomena metabolism and nutrition Opsonin Proteins Fusion protein In vitro Infectious Diseases Pneumococcal vaccine Vaccine Fimbriae Bacterial biology.protein bacteria Molecular Medicine Female Immunization Fimbriae Proteins Rabbits Antibody |
| Zdroj: | Vaccine. 30(7) |
| ISSN: | 1873-2518 |
| Popis: | RrgB321, a fusion protein of the three Streptococcus pneumoniae pilus-1 backbone RrgB variants, is protective in vivo against pilus islet 1 (PI-1) positive pneumococci. In addition, antibodies to RrgB321 mediate a complement-dependent opsonophagocytosis of PI-1 positive strains at levels comparable to those obtained with antisera against glycoconjugate vaccines. In the pneumococcus, pilus-1 displays a biphasic expression pattern, with different proportions of two bacterial phenotypes, one expressing and one not expressing the pilus-1. These two populations can be stably separated in vitro giving rise to the enriched high (H) and low (L) pilus expressing populations. In this work we demonstrate that: (i) the opsonophagocytic killing mediated in vitro by RrgB321antisera is strictly dependent on the pilus expression ratio of the strain used; (ii) during the opsonophagocytosis assay pilus-expressing pneumococci are selectively killed, and (iii) no switch towards the pilus non-expressing phenotype can be observed. Furthermore, in sepsis and pneumonia models, mice immunized with RrgB321 are significantly protected against challenge with either the H or the L pilus-expressing population of strains representative of the three RrgB variants. This suggests that the pilus-1 expression is not down-regulated, and also that the expression of the pilus-1 could be up-regulated in vivo . In conclusion, these data provide evidence that RrgB321 is protective against PI-1 positive strains regardless of their pilus expression level, and support the rationale for the inclusion of this fusion protein into a multi-component protein-based pneumococcal vaccine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect