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Journal of Virology, January 2001, p. 645-653, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.645-653.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Immunogenicity and Protective Efficacy of Oligomeric Human Immunodeficiency Virus Type 1 gp140

Patricia L. Earl,^1,* Wataru Sugiura,^1, David C. Montefiori,² Christopher C. Broder,^1, Susan A. Lee,¹ Carl Wild,³ Jeffrey Lifson,⁴ and Bernard Moss¹

Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0455¹; Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710²; Panacos Pharmaceuticals, Gaithersburg, Maryland 20877³; and Retroviral Pathogenesis Laboratory, AIDS Vaccine Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702⁴

Received 12 July 2000/Accepted 9 October 2000

The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.

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^* Corresponding author. Mailing address: Laboratory of Viral Diseases, National Institutes of Health, Building 4, Room 236, 4 Center Dr., Bethesda, MD 20892-0455. Phone: (301) 402-4112. Fax: (301) 480-1147. E-mail: pearl{at}nih.gov.

Present address: AIDS Research Center, The Second Research Group, National Institute of Infectious Diseases, 4-7-1 Gakuenn, Musashimurayama, Tokyo 2080011, Japan.

Present address: Department of Microbiology and Immunology, F. Edward Hebert School of Medicine, Uniformed Services University, Bethesda, MD 20814-4799.

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Journal of Virology, January 2001, p. 645-653, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.645-653.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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