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Characterization of protective immune responses induced by pneumococcal surface protein A in fusion with pneumolysin derivatives.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (3), pp. e59605. Date of Electronic Publication: 2013 Mar 22. - Publication Year :
- 2013
-
Abstract
- Pneumococcal surface protein A (PspA) and Pneumolysin derivatives (Pds) are important vaccine candidates, which can confer protection in different models of pneumococcal infection. Furthermore, the combination of these two proteins was able to increase protection against pneumococcal sepsis in mice. The present study investigated the potential of hybrid proteins generated by genetic fusion of PspA fragments to Pds to increase cross-protection against fatal pneumococcal infection. Pneumolisoids were fused to the N-terminus of clade 1 or clade 2 pspA gene fragments. Mouse immunization with the fusion proteins induced high levels of antibodies against PspA and Pds, able to bind to intact pneumococci expressing a homologous PspA with the same intensity as antibodies to rPspA alone or the co-administered proteins. However, when antibody binding to pneumococci with heterologous PspAs was examined, antisera to the PspA-Pds fusion molecules showed stronger antibody binding and C3 deposition than antisera to co-administered proteins. In agreement with these results, antisera against the hybrid proteins were more effective in promoting the phagocytosis of bacteria bearing heterologous PspAs in vitro, leading to a significant reduction in the number of bacteria when compared to co-administered proteins. The respective antisera were also capable of neutralizing the lytic activity of Pneumolysin on sheep red blood cells. Finally, mice immunized with fusion proteins were protected against fatal challenge with pneumococcal strains expressing heterologous PspAs. Taken together, the results suggest that PspA-Pd fusion proteins comprise a promising vaccine strategy, able to increase the immune response mediated by cross-reactive antibodies and complement deposition to heterologous strains, and to confer protection against fatal challenge.
- Subjects :
- Animals
Bacterial Proteins genetics
Female
Mice
Mice, Inbred BALB C
Pneumococcal Vaccines genetics
Recombinant Fusion Proteins genetics
Streptolysins genetics
Bacterial Proteins immunology
Bacterial Proteins metabolism
Pneumococcal Vaccines immunology
Pneumococcal Vaccines metabolism
Recombinant Fusion Proteins immunology
Recombinant Fusion Proteins metabolism
Streptolysins immunology
Streptolysins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23533636
- Full Text :
- https://doi.org/10.1371/journal.pone.0059605