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J Virol, March 1998, p. 2253-2258, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Enhanced Virus Clearance by Early Inducible Lymphocytic Choriomeningitis Virus-Neutralizing Antibodies in Immunoglobulin-Transgenic Mice

Peter Seiler,^1,* Ulrich Kalinke,¹ Thomas Rülicke,² Etienne M. Bucher,¹ Christian Böse,^1, Rolf M. Zinkernagel,¹ and Hans Hengartner¹

Department of Pathology, Institute of Experimental Immunology, University of Zurich,¹ and Biologisches Zentrallabor, University Hospital Zurich,² CH 8091 Zurich, Switzerland

Received 1 October 1997/Accepted 24 November 1997

Following infection of mice with lymphocytic choriomeningitis virus (LCMV), virus-neutralizing antibodies appear late, after 30 to 60 days. Such neutralizing antibodies play an important role in protection against reinfection. To analyze whether a neutralizing antibody response which developed earlier could contribute to LCMV clearance during the acute phase of infection, we generated transgenic mice expressing LCMV-neutralizing antibodies. Transgenic mice expressing the immunoglobulin µ heavy chain of the LCMV-neutralizing monoclonal antibody KL25 (H25 transgenic mice) mounted LCMV-neutralizing immunoglobulin M (IgM) serum titers within 8 days after infection. This early inducible LCMV-neutralizing antibody response significantly improved the host's capacity to clear the infection and did not cause an enhancement of disease after intracerebral (i.c.) LCMV infection. In contrast, mice which had been passively administered LCMV-neutralizing antibodies and transgenic mice exhibiting spontaneous LCMV-neutralizing IgM serum titers (HL25 transgenic mice expressing the immunoglobulin µ heavy and the  light chain) showed an enhancement of disease after i.c. LCMV infection. Thus, early-inducible LCMV-neutralizing antibodies can contribute to viral clearance in the acute phase of the infection and do not cause antibody-dependent enhancement of disease.

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^* Corresponding author. Mailing address: Institute of Experimental Immunology, Department of Pathology, University Hospital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland. Phone: 41-1-255 2989. Fax: 41-1-255 4420. E-mail: sep{at}pathol.unizh.ch.

Present address: Johns Hopkins University, Department of Neuroscience, Baltimore, MD 21205.

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