Glycolytic enzymes associated with the cell surface of Streptococcus pneumoniae are antigenic in humans and elicit protective immune responses in the mouse

Abstract

SUMMARYStreptococcus pneumoniae is a leading cause of otitis media, sinusitis, pneumonia, bacteraemia and meningitis worldwide. The drawbacks associated with the limited number of various capsular polysaccharides that can be included in the polysaccharide-based vaccines focuses much attention on pneumococcal proteins as vaccine candidates. We extracted an enriched cell wall fraction from S. pneumoniae WU2. Approximately 150 soluble proteins could be identified by 2D gel electrophoresis. The proteins were screened by 2D-Western blotting using sera that were obtained longitudinally from children attending day-care centres at 18, 30 and 42 months of age and sera from healthy adult volunteers. The proteins were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Seventeen proteins were antigenic in children and adults, of which 13 showed an increasing antibody response with age in all eight children analysed. Two immunogenic proteins, fructose-bisphosphate aldolase (FBA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a control protein with known low immunogenicity, heat shock protein 70 (DnaK), were expressed in Escherichia coli , purified and used to immunize mice. Mouse antibodies elicited to the recombinant (r) FBA and rGAPDH were cross-reactive with several genetically unrelated strains of different serotypes and conferred protection to respiratory challenge with virulent pneumococci. In addition, the FBA used in this study (NP_345117) does not have a human ortholog and warrants further investigation as a candidate for a pneumococcal vaccine. In conclusion, the immunoproteomics based approach utilized in the present study appears to be a suitable tool for identification of novel S. pneumoniae vaccine candidates.

Immunoprotection of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Lactococcus garvieae against Lactococcosis in tilapia

“…Those studies also observed GAPDH and other common antigens found in L. garvieae stains (Shin et al, 2007(Shin et al, , 2009. Moreover, despite studies citing GAPDH as a promising vaccine to protect against Edwardsiella tarda, Vibrio anguillarum and S. pneumonia (Ling et al, 2004;Liu et al, 2005Liu et al, , 2007, efficacy of the GAPDH vaccine from L. garvieae has not been investigated.…”

“…GAPDH is a potential vaccine for protecting against Edwardsiella tarda and Streptococcus pneumonia (Ling et al, 2004;Liu et al, 2005). Protective in several ways, GAPDH may protect antigenicity against other pathogenic bacteria in fish .…”

Conserved anchorless surface proteins as group A streptococcal vaccine candidates

“…GAS α-enolase shares 49% identity with human α-enolase), which raises concern for autoimmune consequences [24]. For further characterization we chose three candidates that are not represented in the human proteome and do not share significant amino acid sequence identity with other human proteins as determined by BLAST-P interrogation (Supplementary Table 1): arginine deiminase (ADI) [25,26] and trigger factor (TF) [27,28], which are potential GAS virulence determinants, and fructose bisphosphate aldolase (FBA), which affords vaccine protection against Streptococcus pneumoniae [29]. All three enzymes lack N-terminal signal sequences and C-terminal cell wall anchors [7].…”

YidC1 and YidC2 are functionally distinct proteins involved in protein secretion, biofilm formation and cariogenicity of Streptococcus mutans

“…GAPDH, as well as a number of other cytoplasmic proteins, has been found on the surface of S. mutans and other streptococci (Henderson & Martin, 2011;Ling et al, 2004;Severin et al, 2007). An investigation by Biswas & Biswas (2005) found that deletion of the HtrA extracellular protease/chaperone resulted in increased levels of extracellular GAPDH in culture media.…”