Evasion of protective immunity by Borrelia burgdorferi by truncation of outer surface protein B.
We analyzed variability in outer surface protein B (OspB) from Borrelia burgdorferi (Bb), the causative agent of Lyme disease, to determine how Bb escapes immune destruction. We have shown that vaccination with OspB from Bb strain B31 protected mice from infection with Bb B31 but not against Bb N40. The present study demonstrates that Bb N40 spirochetes which evade vaccination immunity to OspB have a truncated form of OspB, due to a TAA stop codon at nucleotide 577. In contrast, Bb N40 spirochetes that express full-length OspB are unable to infect mice immunized with OspB, analogous to our previous studies with Bb B31. Mapping of the OspB antibody response shows that epitopes in the C terminus of OspB are surface-exposed and bind protective monoclonal and polyclonal antibodies. This suggests that the C terminus of OspB is important for eliciting a protective immune response to OspB. Truncation or modification of outer surface proteins that do not bind protective antibody may be a means by which Bb evades host defenses.
Fikrig
E
E
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Tao
H
H
Kantor
F S
FS
Barthold
S W
SW
Flavell
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D000939:Epitopes / Q000032:analysis; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D005798:Genes, Bacterial; D006801:Humans; D008193:Lyme Disease / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D015183:Restriction Mapping; D013987:Ticks / Q000382:microbiology; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D003062:Codon; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C077030:OspB protein, Borrelia burgdorferi