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Journal of Virology, April 2002, p. 3511-3521, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3511-3521.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins

Christoph Grundner,1 Tajib Mirzabekov,1,2,{dagger} Joseph Sodroski,1,2,3 and Richard Wyatt1,4*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,1 Department of Pathology,2 Division of AIDS, Department of Medicine, Harvard Medical School,4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021153

Received 19 September 2001/ Accepted 4 January 2002

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein gp120 mediates receptor binding and is the major target for neutralizing antibodies. A broadly neutralizing antibody response is likely to be a critical component of the immune response against HIV-1. Although antibodies against monomeric gp120 are readily elicited in immunized individuals, these antibodies are inefficient in neutralizing primary HIV-1 isolates. As a chronic pathogen, HIV-1 has evolved to avoid an optimal host response by a number of immune escape mechanisms. Monomeric gp120 that has dissociated from the functional trimer presents irrelevant epitopes that are not accessible on functional trimeric envelope glycoproteins. The resulting low level of antigenic cross-reactivity between monomeric gp120 and the functional spike may contribute to the inability of monomeric gp120 to elicit broadly neutralizing antibodies. Attempts to generate native, trimeric envelope glycoproteins as immunogens have been frustrated by both the lability of the gp120-gp41 interaction and the weak association between gp120 subunits. Here, we present solid-phase HIV-1 gp160{Delta}CT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins in a physiologic membrane setting. We present data that indicate that the gp160{Delta}CT glycoproteins on PLs are trimers and are recognized by several relevant conformational ligands in a manner similar to that for gp160{Delta}CT oligomers expressed on the cell surface. The PLs represent a significant advance over present envelope glycoprotein formulations as candidate immunogens for HIV vaccine design and development.

* Corresponding author. Present address: Structural Virology Section, Vaccine Research Center, National Institutes of Health, 40 Convent Dr., Bldg. 40, Room 4512, Bethesda, MD 20892-3005. Phone: (301) 594-8690. Fax: (301) 480-0274. E-mail: richardwyatt{at}nih.gov.

{dagger} Present address: Praecis Pharmaceuticals, Waltham, MA 02451-1420.

Journal of Virology, April 2002, p. 3511-3521, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3511-3521.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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