Immunization of Healthy Adults With a Single Recombinant Pneumococcal Surface Protein A (PspA) Variant Stimulates Broadly Cross-Reactive Antibodies to Heterologous PspA Molecules

Vaccine. 2000 Mar 6;18(17):1743-54. doi: 10.1016/s0264-410x(99)00530-7.

Abstract

Pneumococcal surface protein A (PspA) is a highly variable protein found on all strains of pneumococci. To be successful, a PspA-based vaccine for S. pneumoniae must induce antibodies that are broadly cross-reactive. To address whether cross-reactive antibodies could be induced in man, we evaluated serum from adults immunized with recombinant clade 2 PspA from strain Rx1. Immunization with 5-125 microg rPspA lead to a significant increase in circulating anti-PspA antibodies, as well as antibodies reactive to heterologous rPspA molecules. Increased binding of post-immune sera to 37 pneumococcal strains expressing a variety of PspA and capsule types was observed, versus pre-immune sera. The extent of cross-clade reactivity of human anti-rPspA followed roughly the amount of sequence homology to the non-clade 2 antigens. It is hypothesized that priming of humans by natural exposure to S. pneumoniae contributes to the breadth of the cross-reactivity of antibody to PspA.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Bacterial / blood
  • Antibody Formation / drug effects
  • Antibody Formation / immunology*
  • Antibody Specificity
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Binding, Competitive / immunology
  • Cross Reactions / immunology
  • Double-Blind Method
  • Humans
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Middle Aged
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / immunology
  • Vaccines, Synthetic / administration & dosage*
  • Vaccines, Synthetic / immunology*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Immunoglobulin G
  • Recombinant Proteins
  • Vaccines, Synthetic
  • pneumococcal surface protein A