Studies on the different conditions for rabies virus neutralization by monoclonal antibodies #1-46-12 and #7-1-9.
Virus-neutralizing activity of two monoclonal antibodies (mAbs), #7-1-9 and #1-46-12, against rabies virus glycoprotein (G) was compared. Although these mAbs affected the virion's ability to bind to host cells similarly, a big difference was found in the titres of virus neutralization (1:7132 and 1:32 for mAbs #1-46-12 and #7-1-9, respectively, at a concentration of 10 micro g protein/ml). Although no big difference in virion-binding affinity between the two mAbs was found, the number of antibodies required for virus neutralization was very low, </=20 molecules for mAb #1-46-12 and >/=250 molecules for mAb #7-1-9. In the latter case, the mAbs cover a major part of the virion surface and cause steric hindrance of viral receptor-binding activity. The infectivity of an epitope-preserved escape mutant virus (R-61) was not affected by the binding of high numbers of mAb #1-46-12 to the virion, which implies that mAb binding does not mask the receptor-binding site of the viral spikes. Based on these results, it is hypothesized that mAb #1-46-12 affected virus infectivity by a mechanism different from covering the virion spikes. Possible virus-neutralizing mechanisms by low numbers of mAb #1-46-12 in comparison to that of mAb #7-1-9 are discussed.
Irie
Takashi
T
Department of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan1.
Kawai
Akihiko
A
Department of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan1.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D009500:Neutralization Tests; D011820:Rabies virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014771:Virion / Q000276:immunology; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral