scholarly journals Development of Antibodies to PspA Families 1 and 2 in Children after Exposure to Streptococcus pneumoniae

2008 ◽  
Vol 15 (10) ◽  
pp. 1529-1535 ◽  
Author(s):  
Merit M. Melin ◽  
Susan K. Hollingshead ◽  
David E. Briles ◽  
Mika I. Lahdenkari ◽  
Terhi M. Kilpi ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Acute Otitis Media ◽  
Surface Protein ◽  
High Serum ◽  
Pneumococcal Carriage ◽  
Low Concentrations ◽  
History Of ◽  
Important Virulence Factor ◽  
History Of Culture

ABSTRACT Pneumococcal surface protein A (PspA) is an important virulence factor of Streptococcus pneumoniae. PspA exists as two major families, which include variable but serologically cross-reactive proteins. Previous studies with a family 1 PspA antigen suggested that children develop low concentrations of anti-PspA after pneumococcal carriage or infection. In this study, antibody to PspA families 1 and 2 was measured by an enzyme immunoassay of the serum and saliva of children with a history of culture-proven pneumococcal colonization and/or acute otitis media and in the serum and saliva of adults. The PspA families of the pneumococcal strains isolated from children were determined. The majority of the children had high serum and salivary anti-PspA concentrations to the PspA family they had encountered and low concentrations to the other, whereas adults had high antibody concentrations to both PspA families, both in serum and in saliva. The results suggest that children have a relatively family-specific antibody response to the PspA family they have been exposed to and that any PspA vaccine for children should contain members of both major PspA families.

scholarly journals Distribution of Pneumococcal Surface Protein A Families 1 and 2 among Streptococcus pneumoniae Isolates from Children in Finland Who Had Acute Otitis Media or Were Nasopharyngeal Carriers

2008 ◽  
Vol 15 (10) ◽  
pp. 1555-1563 ◽  
Author(s):  
Merit M. Melin ◽  
Susan K. Hollingshead ◽  
David E. Briles ◽  
William P. Hanage ◽  
Mika Lahdenkari ◽  
...  
Keyword(s):  
Otitis Media ◽  
Vaccine Candidate ◽  
Protein A ◽  
Acute Otitis Media ◽  
Surface Protein ◽  
Pneumococcal Carriage ◽  
Middle Ear Fluid ◽  
Cell Enzyme ◽  
Variable Surface ◽  
Sequence Types

ABSTRACT PspA is a structurally variable surface protein important to the virulence of pneumococci. PspAs are serologically cross-reactive and exist as two major families. In this study, we determined the distribution of PspA families 1 and 2 among pneumococcal strains isolated from the middle ear fluid (MEF) of children with acute otitis media and from nasopharyngeal specimens of children with pneumococcal carriage. We characterized the association between the two PspA families, capsular serotypes, and multilocus sequence types (STs) of the pneumococcal isolates. MEF isolates (n = 201) of 109 patients and nasopharyngeal isolates (n = 173) of 49 children were PspA family typed by whole-cell enzyme immunoassay (EIA). Genetic typing (PCR) of PspA family was done for 60 isolates to confirm EIA typing results. The prevalences of PspA families 1 and 2 were similar among pneumococci isolated from MEF (51% and 45%, respectively) and nasopharyngeal specimens (48% each). Isolates of certain capsule types as well as isolates of certain STs showed statistical associations with either family 1 or family 2 PspA. Pneumococci from seven children with multiple pneumococcal isolates appeared to express serologically different PspA families in different isolates of the same serotype; in three of the children the STs of the isolates were the same, suggesting that antigenic changes in the PspA expressed may have taken place. The majority of the isolates (97%) belonged to either PspA family 1 or family 2, suggesting that a combination including the two main PspA families would make a good vaccine candidate.

scholarly journals Diversity of PspA: Mosaic Genes and Evidence for Past Recombination in Streptococcus pneumoniae

2000 ◽  
Vol 68 (10) ◽  
pp. 5889-5900 ◽  
Author(s):  
Susan K. Hollingshead ◽  
Robert Becker ◽  
David E. Briles
Keyword(s):  
Streptococcus Pneumoniae ◽  
Gene Pair ◽  
Protein A ◽  
Surface Protein ◽  
Intragenic Recombination ◽  
Mosaic Pattern ◽  
Protective Antibodies ◽  
History Of ◽  
Species Comparisons ◽  
Sequence Relationships

ABSTRACT Pneumococcal surface protein A (PspA) is a serologically variable protein of Streptococcus pneumoniae. Twenty-four diverse alleles of the pspA gene were sequenced to investigate the genetic basis for serologic diversity and to evaluate the potential of diversity to have an impact on PspA's use in human vaccination. The 24pspA gene sequences from unrelated strains revealed two major allelic types, termed “families,” subdivided into clades. A highly mosaic gene structure was observed in which individual mosaic sequence blocks in PspAs diverged from each other by over 20% in many cases. This level of divergence exceeds that observed for blocks in the penicillin-binding proteins of S. pneumoniae or in many cross-species comparisons of gene loci. Conversely, because the mosaic pattern is so complex, each pair of pspA genes also has numerous shared blocks, but the position of conserved blocks differs from gene pair to gene pair. A central region of pspA, important for eliciting protective antibodies, was found in six clades, which each diverge from the other clades by >20%. Sequence relationships among the 24 alleles analyzed over three windows were discordant, indicating that intragenic recombination has occurred within this locus. The extensive recombination which generated the mosaic pattern seen in the pspA locus suggests that natural selection has operated in the history of this gene locus and underscores the likelihood that PspA may be important in the interaction between the pneumococcus and its human host.

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 Differential PsaA-, PspA-, PspC-, and PdB-Specific Immune Responses in a Mouse Model of Pneumococcal Carriage

2005 ◽  
Vol 73 (2) ◽  
pp. 1006-1013 ◽  
Author(s):  
Ravichandran Palaniappan ◽  
Shailesh Singh ◽  
Udai P. Singh ◽  
Senthil Kumar K. Sakthivel ◽  
Edwin W. Ades ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protein A ◽  
Serum Antibody ◽  
Surface Protein ◽  
Interleukin 4 ◽  
Necrosis Factor Alpha ◽  
Cervical Lymph Nodes ◽  
Pneumococcal Carriage ◽  
Macrophage Colony ◽  
Antibody Levels

ABSTRACT Larger numbers of pneumococci were detected in the nasal tract compared to the lung, cervical lymph nodes, and spleen 1, 2, 4, 7, 14, and 21 days after nasal challenge with Streptococcus pneumoniae strain EF3030. In this mouse model of pneumococcal carriage, peripheral S. pneumoniae pneumococcal surface adhesin A (PsaA)-specific humoral responses (immunoglobulin G2a [IgG2a] ≫ IgG1 = IgG2b > IgG3) were significantly higher than pneumococcal surface protein A (PspA)-specific, genetic toxoid derivative of pneumolysin (PdB)-specific, or pneumococcal surface protein C (PspC)-specific serum antibody levels. However, PspA-specific mucosal IgA antibody levels were significantly higher than those against PsaA, PdB, and PspC. In general, both PsaA- and PspA-specific lung-, cervical lymph node-, nasal tract-, and spleen-derived CD4+ T-cell cytokine (interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha) and proliferative responses were higher than those for either PspC or PdB. Taken together, these findings suggest that PsaA- and PspA-specific mucosal responses as well as systemic humoral and T helper cell cytokine responses are predominantly yet differentially induced during pneumococcal carriage.

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
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