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

被引:170
作者
Nabors, GS
Braun, PA
Herrmann, DJ
Heise, ML
Pyle, DJ
Gravenstein, S
Schilling, M
Ferguson, LM
Hollingshead, SK
Briles, DE
Becker, RS
机构
[1] Aventis Pasteur, Swiftwater, PA 18370 USA
[2] Eastern Virginia Med Sch, Norfolk, VA 23507 USA
[3] Univ Alabama, Birmingham, AL 35294 USA
关键词
PspA; Streptococcus; pneumococcus;
D O I
10.1016/S0264-410X(99)00530-7
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 mu g 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. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1743 / 1754
页数:12
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