scholarly journals Identification of the Targets of Cross-Reactive Antibodies Induced by Streptococcus pneumoniae Colonization

2010 ◽  
Vol 78 (5) ◽  
pp. 2231-2239 ◽  
Author(s):  
Aoife M. Roche ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Surface Protein ◽  
Wild Type ◽  
Modest Contribution ◽  
Heterologous Challenge ◽  
Human Sera ◽  
Maturation Protein ◽  
Type Strains ◽  
Major Target

ABSTRACTMuch of the efficacy of current pneumococcal conjugate vaccines lies in their ability to decrease carriage of vaccine serotypes in the population. Novel and more-broadly acting vaccines would also need to target carriage in order to be as effective. We have previously shown that model murine carriage ofStreptococcus pneumoniaecan elicit antibody-dependent immunity and can protect against a virulent heterologous challenge strain. This study set out to identifyS. pneumoniaesurface antigens that may elicit cross-reactive antibodies following colonization. Western blot analysis using sera from colonized mice identified the previously characterized immunogens pneumococcal surface protein A (PspA), putative proteinase maturation protein A (PpmA), and pneumococcal surface adhesin A (PsaA) as such antigens. Using flow cytometry, PspA was found to be the major target of surface-bound cross-reactive IgG in sera from TIGR4Δcps-colonized mice, with a modest contribution from PpmA and none from PsaA. In human sera, however, only mutants lacking PpmA were shown to have reduced binding of surface IgG compared to wild-type strains, suggesting that prior exposure toS. pneumoniaein humans may induce PpmA antibodies. We also investigated if cross-reactive antibodies induced by these antigens may be cross-protective against carriage. Despite the immunogenicity of PspA, PpmA, and PsaA, mice were still protected following colonization with mutants lacking these antigens, suggesting they are not necessary for cross-protection induced by carriage. Our findings suggest that a whole-organism approach may be needed to broadly diminish carriage.

scholarly journals Streptococcus pneumoniae Surface Protein PcpA Elicits Protection against Lung Infection and Fatal Sepsis

2008 ◽  
Vol 76 (6) ◽  
pp. 2767-2776 ◽  
Author(s):  
David T. Glover ◽  
Susan K. Hollingshead ◽  
David E. Briles
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Surface Protein ◽  
Murine Models ◽  
Wild Type ◽  
Survival Times ◽  
High Manganese ◽  
Subcutaneous Immunization ◽  
Fatal Sepsis ◽  
Manganese Concentrations

ABSTRACTPrevious studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence ofStreptococcus pneumoniae, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewerS. pneumoniaecells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4- to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.

scholarly journals DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein

2006 ◽  
Vol 55 (4) ◽  
pp. 375-378 ◽  
Author(s):  
Daniela M. Ferreira ◽  
Eliane N. Miyaji ◽  
Maria Leonor S. Oliveira ◽  
Michelle Darrieux ◽  
Ana Paula M. Arêas ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Recombinant Protein ◽  
Dna Vaccines ◽  
Protein A ◽  
Surface Protein ◽  
Humoral Response ◽  
Cost Effective ◽  
Promising Candidate ◽  
Pneumococcal Surface Protein A ◽  
Antibody Levels

Pneumococcal surface protein A (PspA) is a promising candidate for the development of cost-effective vaccines against Streptococcus pneumoniae. In the present study, BALB/c mice were immunized with DNA vaccine vectors expressing the N-terminal region of PspA. Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol. However, both immunogens elicited similar levels of protection against intraperitoneal challenge. Furthermore, immunization with exactly the same fragment in the form of a recombinant protein, with aluminium hydroxide as an adjuvant, elicited even higher antibody levels, but this increased humoral response did not correlate with enhanced protection. These results show that DNA vaccines expressing PspA are able to elicit protection levels comparable to recombinant protein, even though total anti-PspA IgG response is considerably lower.

scholarly journals Pneumococcal Surface Protein C Contributes to Sepsis Caused by Streptococcus pneumoniae in Mice

2004 ◽  
Vol 72 (5) ◽  
pp. 3077-3080 ◽  
Author(s):  
Francesco Iannelli ◽  
Damiana Chiavolini ◽  
Susanna Ricci ◽  
Marco Rinaldo Oggioni ◽  
Gianni Pozzi
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein C ◽  
Lethal Dose ◽  
Surface Protein ◽  
Infection Model ◽  
Wild Type ◽  
Mutant Strains ◽  
Type 3

ABSTRACT The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis by Streptococcus pneumoniae was investigated in a murine infection model. The pspC gene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice. The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type. Our findings indicate that PspC affords a decisive contribution to sepsis development.

scholarly journals DprA-Dependent Exit from the Competent State Regulates Multifaceted Streptococcus pneumoniae Virulence

2019 ◽  
Vol 87 (11) ◽  
Author(s):  
Jingjun Lin ◽  
Gee W. Lau
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Cell Separation ◽  
Protein A ◽  
Wild Type ◽  
Content Type ◽  
Cellular Processes ◽  
Virulence Attenuation ◽  
Specific Induction ◽  
Competence System

ABSTRACT Streptococcus pneumoniae (pneumococcus) causes multiple infectious diseases. The pneumococcal competence system facilitates genetic transformation, spreads antibiotic resistance, and contributes to virulence. DNA-processing protein A (DprA) regulates the exit of pneumococcus from the competent state. Previously, we have shown that DprA is important in both bacteremia and pneumonia infections. Here, we examined the mechanisms of virulence attenuation in a ΔdprA mutant. Compared to the parental wild-type D39, the ΔdprA mutant enters the competent state when exposed to lower concentrations of the competence-stimulating peptide CSP1. The ΔdprA mutant overexpresses ComM, which delays cell separation after division. Additionally, the ΔdprA mutant overexpresses allolytic factors LytA, CbpD, and CibAB and is more susceptible to detergent-triggered lysis. Disabling of the competent-state-specific induction of ComM and allolytic factors compensated for the virulence loss in the ΔdprA mutant, suggesting that overexpression of these factors contributes to virulence attenuation. Finally, the ΔdprA mutant fails to downregulate the expression of multiple competence-regulated genes, leading to the excessive energy consumption. Collectively, these results indicate that an inability to properly exit the competent state disrupts multiple cellular processes that cause virulence attenuation in the ΔdprA mutant.

scholarly journals Determination of phenotypes and pneumococcal surface protein A family types of Streptococcus pneumoniae from Malaysian healthy children

2013 ◽  
Vol 46 (3) ◽  
pp. 180-186 ◽  
Author(s):  
Masura Mohd Yatim ◽  
Siti Norbaya Masri ◽  
Mohd Nasir Mohd Desa ◽  
Niazlin Mohd Taib ◽  
Syafinaz Amin Nordin ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Surface Protein ◽  
Healthy Children ◽  
Pneumococcal Surface Protein A ◽  
Family Types

scholarly journals Immunization of Mice with Combinations of Pneumococcal Virulence Proteins Elicits Enhanced Protection against Challenge with Streptococcus pneumoniae

2000 ◽  
Vol 68 (5) ◽  
pp. 3028-3033 ◽  
Author(s):  
A. David Ogunniyi ◽  
Rebekah L. Folland ◽  
David E. Briles ◽  
Susan K. Hollingshead ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Metal Binding ◽  
Protein A ◽  
Surface Protein ◽  
Active Immunization ◽  
Survival Times ◽  
Virulence Proteins ◽  
Virulent Type ◽  
Vaccine Potential ◽  
High Doses

ABSTRACT The vaccine potential of a combination of three pneumococcal virulence proteins was evaluated in an active-immunization–intraperitoneal-challenge model in BALB/c mice, using very high challenge doses of Streptococcus pneumoniae. The proteins evaluated were a genetic toxoid derivative of pneumolysin (PdB), pneumococcal surface protein A (PspA), and a 37-kDa metal-binding lipoprotein referred to as PsaA. Mice immunized with individual proteins or combinations thereof were challenged with high doses of virulent type 2 or type 4 pneumococci. The median survival times for mice immunized with combinations of proteins, particularly PdB and PspA, were significantly longer than those for mice immunized with any of the antigens alone. A similar effect was seen in a passive protection model. Thus, combinations of pneumococcal proteins may provide the best non-serotype-dependent protection against S. pneumoniae.

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