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J Virol, April 1998, p. 3427-3431, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Neutralizing Antibodies in Sera from Macaques Infected with Chimeric Simian-Human Immunodeficiency Virus Containing the Envelope Glycoproteins of either a Laboratory-Adapted Variant or a Primary Isolate of Human Immunodeficiency Virus Type 1

David C. Montefiori,1,* Keith A. Reimann,2 Michael S. Wyand,3 Kelledy Manson,3 Mark G. Lewis,4 Ronald G. Collman,5 Joseph G. Sodroski,6 Dani P. Bolognesi,1 and Norman L. Letvin2

Department of Surgery, Duke University Medical Center, Durham, North Carolina1; Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center,2 and Dana-Farber Cancer Institute,6 Harvard Medical School, Boston, and GTC Mason Laboratories, Worcester,3 Massachusetts; Henry M. Jackson Foundation, Rockville, Maryland4; and Division of Pulmonary and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania5

Received 27 August 1997/Accepted 6 December 1997

The magnitude and breadth of neutralizing antibodies raised in response to infection with chimeric simian-human immunodeficiency virus (SHIV) in rhesus macaques were evaluated. Infection with either SHIV-HXB2, SHIV-89.6, or SHIV-89.6PD raised high-titer neutralizing antibodies to the homologous SHIV (SHIV-89.6P in the case of SHIV-89.6PD-infected animals) and significant titers of neutralizing antibodies to human immunodeficiency virus type 1 (HIV-1) strains MN and SF-2. With few exceptions, however, titers of neutralizing antibodies to heterologous SHIV were low or undetectable. The antibodies occasionally neutralized heterologous primary isolates of HIV-1; these antibodies required >40 weeks of infection to reach detectable levels. Notable was the potent neutralization of the HIV-1 89.6 primary isolate by serum samples from SHIV-89.6-infected macaques. These results demonstrate that SHIV-HXB2, SHIV-89.6, and SHIV-89.6P possess highly divergent, strain-specific neutralization epitopes. The results also provide insights into the requirements for raising neutralizing antibodies to primary isolates of HIV-1.

* Corresponding author. Mailing address: Department of Surgery, Duke University Medical Center, Box 2926, Durham, NC 27710. Phone: (919) 684-5278. Fax: (919) 684-4288. E-mail: monte005{at}mc.duke.edu.




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