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J Virol, April 1998, p. 3475-3478, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

CD4-Immunoglobulin G2 Protects Hu-PBL-SCID Mice against Challenge by Primary Human Immunodeficiency Virus Type 1 Isolates

Marie-Claire Gauduin,1,dagger Graham P. Allaway,2,Dagger William C. Olson,2 Raymond Weir,1 Paul J. Maddon,2 and Richard A. Koup1,*

The Aaron Diamond AIDS Research Center and The Rockefeller University, New York, New York 10016,1 and Progenics Pharmaceuticals Inc., Tarrytown, New York 105912

Received 11 September 1997/Accepted 9 December 1997

CD4-immunoglobulin G2 (IgG2) is a fusion protein comprising human IgG2 in which the Fv portions of both heavy and light chains have been replaced by the V1 and V2 domains of human CD4. Previous studies found that CD4-IgG2 potently neutralizes a broad range of primary human immunodeficiency virus type 1 (HIV-1) isolates in vitro and ex vivo. The current report demonstrates that CD4-IgG2 protects against infection by primary isolates of HIV-1 in vivo, using the hu-PBL-SCID mouse model. Passive administration of 10 mg of CD4-IgG2 per kg of body weight protected all animals against subsequent challenge with 10 mouse infectious doses of the laboratory-adapted T-cell-tropic isolate HIV-1LAI, while 50 mg of CD4-IgG2 per kg protected four of five mice against the primary isolates HIV-1JR-CSF and HIV-1AD6. In contrast, a polyclonal HIV-1 Ig fraction exhibited partial protection against HIV-1LAI at 150 mg/kg but no significant protection against the primary HIV-1 isolates. The results demonstrate that CD4-IgG2 effectively neutralizes primary HIV-1 isolates in vivo and can prevent the initiation of infection by these viruses.

* Corresponding author. Mailing address: Department of Internal Medicine, Division of Infectious Disease, University of Texas Southwestern Medical Center, Room Y9.218, 5323 Harry Hines Blvd., Dallas, TX 75235-9113. Phone: (214) 648-2807. Fax: (214) 648-2431. E-mail: rkoup{at}mednet.swmed.edu.

dagger Present address: Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772-9102.

Dagger Present address: Manchester Biosciences Incubator, Manchester M13 9PT, United Kingdom.




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