Protective activity of a murine monoclonal antibody against European bat lyssavirus 1 (EBL1) infection in mice.
A mouse model was designed to test in vivo the efficacy of rabies immune globulins and specific neutralizing monoclonal antibodies to prevent European bat lyssavirus 1 infection. Human or equine rabies immune globulins previously found to contain variable amounts of neutralizing bat lyssavirus crossreactive antibodies were passively transferred to mice receiving intramuscularly a lethal dose of bat lyssavirus type 1. Immune globulins did not protect mice well against bat lyssavirus 1 whereas they reduced the mortality caused by rabies virus. In contrast, mice inoculated with bat lyssavirus 1 or rabies virus survived when passively immunized with bat lyssavirus 1 specific monoclonal antibody (mAb 8-2). This monoclonal antibody, an IgG2 alpha, recognized an epitope located in the antigenic site IIa of rabies glycoprotein. A mutation replacing the lysine 198 by glutamate in a rabies variant abrogated sensitivity to this neutralizing antibody. Because of its broad neutralizing spectrum against wild virus isolates, including European bat lyssaviruses, this monoclonal antibody should be a good candidate for rabies immune globulin replacement. It could improve efficacy of rabies vaccination, used either alone or in conjunction with human rabies immune globulins or monoclonal antibody cocktail to supplement their lack of crossreactivity to European bat lyssavirus 1.
Montaño-Hirose
J A
JA
Unité de la Rage, Institut Pasteur, Paris, France.
Lafage
M
M
Weber
P
P
Badrane
H
H
Tordo
N
N
Lafon
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D001483:Base Sequence; D005260:Female; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000627:therapeutic use; D018114:Lyssavirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008969:Molecular Sequence Data; D011818:Rabies / Q000276:immunology / Q000517:prevention & control; D011819:Rabies Vaccines / Q000627:therapeutic use; D011820:Rabies virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D018353:Rhabdoviridae Infections / Q000382:microbiology / Q000517:prevention & control*; D014774:Virulence
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D011819:Rabies Vaccines