Monoclonal antibody analysis of neutralization and antibody-dependent enhancement of feline infectious peritonitis virus.
Fifty-four monoclonal antibodies (MAbs) to feline infectious peritonitis virus (FIPV) were characterized according to protein specificity, immunoglobulin subclass, virus neutralization, reactivity with different coronaviruses, and ability to induce antibody-dependent enhancement (ADE) of FIPV infection in vitro. The MAbs were found to be specific for one of three structural proteins of FIPV. A total of 47 MAbs were specific for the 205-kDa spike protein (S), 3 MAbs were specific for the 45-kDa nucleocapsid protein (N), and 4 MAbs were specific for the 26- to 28-kDa membrane protein (M). The S-specific MAbs showed various degrees of cross-reactivity with strains of FIPV, feline enteric coronavirus, canine coronavirus, and porcine transmissible gastroenteritis virus. Nineteen S-specific MAbs neutralized FIPV. A total of 15 of the neutralizing MAbs induced ADE, and all but 1 were of the immunoglobulin G2a subclass. The remaining four neutralizing MAbs that did not induce ADE were of the immunoglobulin G1 subclass. Two S-specific MAbs induced ADE but were nonneutralizing. None of the N- or M-specific MAbs was neutralizing or induced ADE. On the basis of the reactivity patterns of the MAbs with FIPV and related coronaviruses, it was concluded that there is a minimum of five neutralizing sites on S. In most instances, neutralizing MAbs were able to induce ADE, demonstrating a direct relationship between neutralization and enhancement. The difference in immunoglobulin subclass between neutralizing MAbs that induced ADE and those that did not induce ADE suggests that there may be a restriction in the immunoglobulin subclasses capable of mediating ADE.
Corapi
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WV
Department of Microbiology, Immunology, and Parasitology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Olsen
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CW
Scott
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FW
D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002213:Capsid / Q000276:immunology; D002415:Cats; D003332:Coronaviridae / Q000276:immunology; D016765:Coronavirus, Feline / Q000276:immunology*; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007114:Immunization; D007074:Immunoglobulin G / Q000145:classification; D008954:Models, Biological; D009154:Mutation; D009500:Neutralization Tests; D011233:Precipitin Tests; D014758:Viral Core Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C064484:spike protein S, Transmissible gastroenteritis virus