Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques.
The identification of HIV envelope structures that generate broadly cross-reactive neutralizing antibodies is a major goal for HIV-vaccine development. In this study, we evaluated one such structure, expressed as either a gp120-CD4 or a gp140-CD4 complex, for its ability to elicit a neutralizing antibody response. In rhesus macaques, covalently crosslinked complexes of soluble human CD4 (shCD4) and HIV-1(IIIB) envelope glycoproteins (gp120 or gp140) generated antibodies that neutralized a wide range of primary HIV-1 isolates regardless of the coreceptor usage or genetic subtype. Ig with cross-reactive neutralizing activity was recovered by affinity chromatography with a chimeric single-chain polypeptide containing sequences for HIV(BaL) gp120 and a mimetic peptide that induces a CD4-triggered envelope structure. These results suggest that covalently crosslinked complexes of the HIV-1 surface envelope glycoprotein and CD4 elicit broadly neutralizing humoral responses that, in part, may be directed against a novel epitope(s) found on the HIV-1 envelope.
Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201, USA.
Timothy
T
Fouts
Karla
K
Godfrey
Kathryn
K
Bobb
David
D
Montefiori
Carl V
CV
Hanson
V S
VS
Kalyanaraman
Anthony
A
DeVico
Ranajit
R
Pal
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000378:metabolism*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D008253:Macaca mulatta; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1