Solid-phase proteoliposomes containing human immunodeficiency virus envelope glycoproteins.
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 gp160DeltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins in a physiologic membrane setting. We present data that indicate that the gp160DeltaCT glycoproteins on PLs are trimers and are recognized by several relevant conformational ligands in a manner similar to that for gp160DeltaCT 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.
Grundner
Christoph
C
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Mirzabekov
Tajib
T
Sodroski
Joseph
J
Wyatt
Richard
R
D000956:Antigens, Viral / Q000096:biosynthesis / Q000737:chemistry*; D015153:Blotting, Western; D002460:Cell Line; D002850:Chromatography, Gel; D005434:Flow Cytometry; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics; D019302:HIV Envelope Protein gp160 / Q000032:analysis; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D011510:Proteolipids / Q000096:biosynthesis / Q000737:chemistry*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics
D000956:Antigens, Viral; D006023:Glycoproteins; D019302:HIV Envelope Protein gp160; D011510:Proteolipids; D014759:Viral Envelope Proteins; C020485:proteoliposomes