Rational selection of broadly cross-reactive family 2 PspA molecules for inclusion in chimeric pneumococcal vaccines
| Autor: | Luciana C. C. Leite, Cibelly Goulart, Michelle Darrieux, Dunia Rodriguez, T.R. Converso |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pneumococcal surface protein A Cross Protection Phagocytosis Complement factor I Cross Reactions Biology Microbiology Pneumococcal Infections Virulence factor Pneumococcal Vaccines Mice 03 medical and health sciences 0302 clinical medicine Bacterial Proteins Animals 030212 general & internal medicine Cloning Molecular Antiserum Antigens Bacterial Mice Inbred BALB C Lactoferrin Immune Sera Antibodies Bacterial Fusion protein Virology Recombinant Proteins Streptococcus pneumoniae 030104 developmental biology Infectious Diseases Lytic cycle Complement C3b Macrophages Peritoneal biology.protein Female |
| Zdroj: | Microbial Pathogenesis. 109:233-238 |
| ISSN: | 0882-4010 |
| Popis: | © 2017 Elsevier Ltd Pneumococcal surface protein A (PspA) is a widely studied pneumococcal protein, exposed at the surface of all strains. It is an important virulence factor, preventing complement deposition as well as inhibiting the lytic effects of lactoferrin over pneumococci. Several studies have investigated the use of PspA as a candidate in alternative pneumococcal vaccines, with great success. However, PspA presents sequence variability – there are six clades, grouped in three families – and PspAs within the same clade exhibit different levels of cross-reactivity. Therefore, the aim of this work was to select, from a panel of eight pneumococcal isolates expressing family 2 PspAs, the molecule with the broadest reactivity within this family. Antisera to these PspA fragments were initially screened by immunoblot against thirteen pneumococcal extracts; the three most cross-reactive antisera were tested for their ability to enhance the deposition of complement factor C3b on the bacterial surface and to promote their phagocytosis in vitro. PspA from strain P490 was the most effective, increasing phagocytosis of all but one pneumococcal isolate. Thus, this molecule was selected for inclusion in chimeric protein-based pneumococcal vaccines. In conclusion, the rational selection of cross-reactive molecules is an important step in the development of vaccines with broad coverage. |
| Databáze: | OpenAIRE |
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