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Journal of Virology, February 2001, p. 1165-1171, Vol. 75, No. 3
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.3.1165-1171.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Improved Elicitation of Neutralizing Antibodies
against Primary Human Immunodeficiency Viruses by Soluble Stabilized
Envelope Glycoprotein Trimers
Xinzhen
Yang,1,2
Richard
Wyatt,1,3 and
Joseph
Sodroski1,2,4,*
Department of Cancer Immunology & AIDS,
Dana-Farber Cancer Institute,1
Department of Pathology2 and
Department of Medicine,3 Harvard Medical
School, and Department of Immunology and Infectious
Diseases, Harvard School of Public Health,4
Boston, Massachusetts 02115
Received 31 July 2000/Accepted 17 October 2000
Human immunodeficiency virus (HIV-1) envelope glycoprotein
subunits, such as the gp120 exterior glycoprotein, typically elicit antibodies that neutralize T-cell-line-adapted (TCLA), but not primary,
clinical isolates of HIV-1. Here we compare the immunogenicity of gp120
and soluble stabilized trimers, which were designed to resemble the
functional envelope glycoprotein oligomers of primary and TCLA HIV-1
strains. For both primary and TCLA virus proteins, soluble stabilized
trimers generated neutralizing antibody responses more efficiently than
gp120 did. Trimers derived from a primary isolate elicited antibodies
that neutralized primary and TCLA HIV-1 strains. By contrast, trimers
derived from a TCLA isolate generated antibodies that neutralized only
the homologous TCLA virus. Thus, soluble stabilized envelope
glycoprotein trimers derived from primary HIV-1 isolates represent
defined immunogens capable of eliciting neutralizing antibodies that
are active against clinically relevant HIV-1 strains.
*
Corresponding author. Mailing address: Department of
Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney St., JFB 824, Boston, MA 02115. Phone: (617) 632-3371. Fax: (617) 632-4338. E-mail: Joseph_Sodroski{at}dfci.harvard.edu.
Journal of Virology, February 2001, p. 1165-1171, Vol. 75, No. 3
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.3.1165-1171.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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