Selection of variant Borrelia burgdorferi isolates from mice immunized with outer surface protein A or B.
A nonclonal population of Borrelia burgdorferi N40 (passage 3) that survived protective immunity following challenge inoculation of outer surface protein (Osp) A- or B-hyperimmunized mice were characterized for the molecular basis of evasion of immunity. Two of six B. burgdorferi isolates, cultured from OspA-immunized mice, had antigenic diversity in the carboxyl terminus of OspA and did not bind to the protective OspA monoclonal antibody designated IXDII. However, OspA-immunized mice challenged with these variants were fully protected. Moreover, B. burgdorferi isolates with a point mutation in ospB, which results in a truncated OspB that does not bind to protective OspB monoclonal antibody 7E6C, were frequently enriched after infection of OspB-immunized mice. These studies suggest that the incomplete efficacy of an OspA- or OspB-based vaccine may be partly due to immunomediated in vivo selective pressure, resulting in the persistence of some spirochetes that do not bind to protective antibodies.
Fikrig
E
E
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA.
Tao
H
H
Barthold
S W
SW
Flavell
R A
RA
D000818:Animals; D000942:Antigens, Bacterial; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000235:genetics*; D003001:Cloning, Molecular; D005260:Female; D005798:Genes, Bacterial; D014644:Genetic Variation; D015151:Immunoblotting; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000276:immunology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014611:Vaccination
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D011994:Recombinant Proteins; C077030:OspB protein, Borrelia burgdorferi