Crosslinked HIV-1 envelope–CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques
AUTOR(ES)
Fouts, Timothy
FONTE
The National Academy of Sciences
RESUMO
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-1IIIB 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 HIVBaL 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=129356Documentos Relacionados
- Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120–CD4–CCR5 complexes
- Poliovirus hybrids expressing neutralization epitopes from variable domains I and IV of the major outer membrane protein of Chlamydia trachomatis elicit broadly cross-reactive C. trachomatis-neutralizing antibodies.
- Rabies Virus-Based Vectors Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Protein Induce a Strong, Cross-Reactive Cytotoxic T-Lymphocyte Response against Envelope Proteins from Different HIV-1 Isolates
- Localization and Characterization of Flavivirus Envelope Glycoprotein Cross-Reactive Epitopes
- Cross-reactive monoclonal antibodies for diagnosis of pneumococcal meningitis.