Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules

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 addre ss 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 mu g rPspA lead to a significant increase in circul ating anti-PspA antibodies, as well as antibodies reactive to heterologous rPspA molecules. Increased binding of post-immune sera to 37 pneumococcal s trains expressing a variety of PspA and capsule types was observed, Versus pre-immune sera. The extent of cross-clade reactivity of human anti-rPspA f ollowed roughly the amount of sequence homology to the non-clade 2 antigens . It is hypothesized that priming of humans by natural exposure to S. pneum oniae contributes to the breadth of the cross-reactivity of antibody to Psp A. (C) 2000 Elsevier Science Ltd. All rights reserved.