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
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Clinical Trial
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Clinical Trial, Phase I
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Controlled Clinical Trial
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Adult
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Animals
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Antibodies, Bacterial / blood
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Antibody Formation / drug effects
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Antibody Formation / immunology*
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Antibody Specificity
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology*
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Binding, Competitive / immunology
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Cross Reactions / immunology
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Double-Blind Method
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Humans
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Immunoglobulin G / blood
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Injections, Intramuscular
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Middle Aged
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Rabbits
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Streptococcus pneumoniae / classification
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Streptococcus pneumoniae / immunology
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Vaccines, Synthetic / administration & dosage*
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Vaccines, Synthetic / immunology*
Substances
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Antibodies, Bacterial
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Antigens, Bacterial
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Bacterial Proteins
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Immunoglobulin G
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Recombinant Proteins
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Vaccines, Synthetic
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pneumococcal surface protein A