Post-exposure treatment with monoclonal antibodies in a retrovirus system: failure to protect cats against feline leukemia virus infection with virus neutralizing monoclonal antibodies.
We have attempted to protect kittens against oronasal infection with FeLV (strain A/Glasgow-1) by treatment with a mixture of two virus-neutralizing (VN) MAbs (IgGl, K) directed against the same epitope on the viral glycoprotein gp70. Ten SPF 9-week-old kittens were infected on day 0 with 10(6) ffu FeLV and subsequently inoculated i.m. with MAbs every 2 days over a 20-day period at different times after infection. The results clearly show that no protection was achieved. It is unlikely that the amount of VN antibodies, the mode and route of their application or the infectious dose of FeLV used can account for the failure to protect cats against infection. Other possibilities which may explain the lack of protective effect are that the restricted epitope specificity of the MAb preparation used may have led to selection of neutralization-resistant virus mutants, or that other mechanisms than virus neutralization (complement-mediated lysis, antibody-dependent cell cytotoxicity), that may be involved in protection, function less efficiently with MAb. However, in the light of our finding that an early anti-idiotypic response is observed in all cats following administration of the MAb preparation, the rapid clearance of anti-FeLV MAb from the circulation is a more likely explanation. The data presented support our hypothesis that by administration of MAb-as compared to polyclonal antibody-a more vigorous anti-idiotypic response is elicited due to the presentation of only a limited set of idiotopes. This potential drawback of rapid clearance of MAbs as a consequence of an anti-idiotypic response might be overcome by the use of mixtures of MAbs resulting in a more heterogeneous set of idiotypic determinants.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000096:biosynthesis / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000032:analysis; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D002415:Cats; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D005256:Leukemia Virus, Feline / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology / Q000517:prevention & control*; D009500:Neutralization Tests
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007130:Immunoglobulin Idiotypes