Mechanisms of monoclonal antibody-mediated protection against virulent Semliki Forest virus

Author:

Boere W A,Benaissa-Trouw B J,Harmsen T,Erich T,Kraaijeveld C A,Snippe H

Abstract

Both neutralizing and nonneutralizing immunoglobulin G2a monoclonal antibodies (MAs) directed against the E2 glycoprotein of Semliki Forest virus (SFV) protected mice prophylactically and therapeutically against virulent SFV infection. The neutralizing MAs, however, conferred protection to mice at lower doses than did nonneutralizing MAs. The antibody-dependent, complement-mediated cytolysis of SFV-infected L cells was effectuated by both kinds of antibodies, but again neutralizing MAs were more effective. Removal of the Fc part of the neutralizing MA UM 5.1 by pepsin digestion resulted in a 100-fold reduction of the neutralization titer (10(4) versus 10(6)) and a complete loss of its capacity to mediate antibody-dependent, complement-mediated cytolysis. Passive protection of infected mice occurred only after administration of relatively high doses of F(ab')2 of MA UM 5.1 (30.0 micrograms versus 0.1 microgram). F(ab')2 fragments prepared from the nonneutralizing MA UM 4.2 had lost their protective capacity completely. Surprisingly, the nonneutralizing MA UM 4.2 retarded virus growth in mouse fibroblasts (L cells), although inhibition was at much higher doses than with the neutralizing MA UM 5.1. Furthermore, both MAs promoted the uptake of virulent SFV in the Fc receptor-bearing WEHI-3 cells. The results suggest that nonneutralizing MAs protect mice not only by antibody-dependent, complement-mediated cytolysis but also by growth inhibition and enhanced uptake of SFV in the nonpermissive macrophages of BALB/c mice. This hypothesis is supported by the absence of viremia in recipients of nonneutralizing MA UM 4.2 at 24 h after infection.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference23 articles.

1. Neutralizing and non-neutralizing monoclonal antibodies to the E, glycoprotein of Semliki Forest virus can protect mice from lethal encephalitis;Boere W. A. M.;J. Gen. Virol.,1983

2. Identification of distinct antigenic determinants on Semliki Forest virus by using monoclonal antibodies with different antiviral activities;Boere W. A. M.;J. Virol.,1984

3. The virulence of original and derived strains of Semliki Forest virus for mice, guinea-pigs and rabbits;Bradish C. J.;J. Gen. Virol.,1971

4. Infection of a macrophage-like cell line, P388D1 with reovirus: effects of immune ascitic fluids and monoclonal antibodies on neutralization and on enhancement of viral growth;Burstin S. J.;J. Immunol.,1983

5. Conformational changes in Sindbis virus El glycoprotein induced by monoclonal antibody binding;Clegg J. C. S.;J. Gen. Virol.,1983

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