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 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.
Nabors
G S
GS
Aventis Pasteur, Discovery Drive, Swiftwater, PA 18370, USA. gary.nabors@aventis.com
Braun
P A
PA
Herrmann
D J
DJ
Heise
M L
ML
Pyle
D J
DJ
Gravenstein
S
S
Schilling
M
M
Ferguson
L M
LM
Hollingshead
S K
SK
Briles
D E
DE
Becker
R S
RS
D000293:Adolescent; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D008875:Middle Aged; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C051592:pneumococcal surface protein A