Recognition of Pneumococcal Isolates by Antisera Raised Against PspA Fragments From Different Clades

J Med Microbiol. 2008 Mar;57(Pt 3):273-278. doi: 10.1099/jmm.0.47661-0.

Abstract

Pneumococcal surface protein A (PspA) is an important vaccine candidate against pneumococcal infections, capable of inducing protection in different animal models. Based on its structural diversity, it has been suggested that a PspA-based vaccine should contain at least one fragment from each of the two major families (family 1, comprising clades 1 and 2, and family 2, comprising clades 3, 4 and 5) in order to elicit broad protection. This study analysed the recognition of a panel of 35 pneumococcal isolates bearing different PspAs by antisera raised against the N-terminal regions of PspA clades 1 to 5. The antiserum to PspA clade 4 was found to show the broadest cross-reactivity, being able to recognize pneumococcal strains containing PspAs of all clades in both families. The cross-reactivity of antibodies elicited against a PspA hybrid including the N-terminal region of clade 1 fused to a shorter and more divergent fragment (clade-defining region, or CDR) of clade 4 (PspA1-4) was also tested, and revealed a strong recognition of isolates containing clades 1, 4 and 5, and weaker reactions with clades 2 and 3. The analysis of serum reactivity against different PspA regions further revealed that the complete N-terminal region rather than just the CDR should be included in an anti-pneumococcal vaccine. A PspA-based vaccine is thus proposed to be composed of the whole N-terminal region of clades 1 and 4, which could also be expressed as a hybrid protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood*
  • Antibodies, Bacterial / immunology*
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / immunology
  • Bacterial Proteins* / isolation & purification
  • Cross Reactions
  • Female
  • Humans
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Pneumococcal Infections / microbiology
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / chemistry
  • Pneumococcal Vaccines / immunology*
  • Recombinant Proteins / immunology
  • Serotyping
  • Streptococcus pneumoniae / classification*
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / isolation & purification

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Pneumococcal Vaccines
  • Recombinant Proteins
  • pneumococcal surface protein A