Abstract
Pneumococcal surface protein A (PspA) is one of the most abundant cell surface protein of Streptococcus pneumoniae (S. pneumoniae). PspA variants are structurally and serologically diverse and help evade complement-mediated phagocytosis of S. pneumoniae, which is essential for its survival in the host. PspA is currently been screened for employment in the generation of more effective (serotype independent) vaccine to overcome the limitations of polysaccharide based vaccines, providing serotype specific immune responses. The cross-protection eliciting regions of PspA localize to the α-helical and proline rich regions. Recent data indicate significant variation in the ability of antibodies induced against the recombinant PspA variants to recognize distinct S. pneumoniae strains. Hence, screening for the identification of the topographical repertoire of B-cell epitopes that elicit cross-protective immune response seems essential in the engineering of a superior PspA-based vaccine. Herein, we revisit epitope identification in PspA and the utility of hybridoma technology in directing the identification of protective epitope regions of PspA that can be used in vaccine research.
Highlights
Streptococcus pneumoniae is a Gram-positive bacterium that asymptomatically colonizes the upper respiratory tract of humans
On one side where serotype diversity of S. pneumoniae complicates the generation of effective vaccines, use of proteins seems advantageous to overcome the limitation with the existing vaccines
Though Pneumococcal surface protein A (PspA) was originally identified by protective monoclonal antibodies raised in CBA/N mice (McDaniel et al, 1984, 1986), cloning of full length PspA gene helped in predicting the complete amino acid sequence of PspA (Yother and Briles, 1992)
Summary
Streptococcus pneumoniae (or pneumococcus) is a Gram-positive bacterium that asymptomatically colonizes the upper respiratory tract of humans. Colonization of the nasopharynx by S. pneumoniae involves adherence of the bacterium to the epithelial surface via different surface molecules (McCullers and Tuomanen, 2001). With more than 90 distinct serotypes, the transition from asymptomatic nasopharyngeal carriage of S. pneumoniae to invasive pneumococcal disease depends on the balance between the host’s defense mechanisms and bacterial adherence ability, nutrition and their replication within the host (Bridy-Pappas et al, 2005). Given serious consideration to limited serotype coverage, there is utmost need to have serotype independent vaccine; generated solely on the protein based strategy or using proteins as candidate in conjugate vaccines, for making them effective against broader range of S. pneumoniae serotypes. On one side where serotype diversity of S. pneumoniae complicates the generation of effective vaccines, use of proteins seems advantageous to overcome the limitation with the existing vaccines. PspA is a promising vaccine candidate because genomes of all S. pneumoniae isolates harbor the pspA gene
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