A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120
| Autor: | Ping Zhu, Robbert P. de Vries, Cheryl Wiley, Dennis R. Burton, Norbert Schülke, Michael Franti, Penny L. Moore, Kenneth H. Roux, David C. Montefiori, Charmagne Cayanan, Pengfei Jiang, Irina Zharkikh, James M. Binley, Emma T. Crooks |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Env
viruses Guinea Pigs V3 loop HIV Antibodies HIV Envelope Protein gp120 Gp41 complex mixtures Neutralization Epitope Article Cell Line 03 medical and health sciences Neutralization Tests Virology VLPs Animals Humans Neutralizing antibody Neutralizing Antibody 030304 developmental biology chemistry.chemical_classification AIDS Vaccines 0303 health sciences biology 030306 microbiology Ligand binding assay HIV virus diseases Molecular biology gp41 HIV Envelope Protein gp41 3. Good health gp120 chemistry biology.protein HIV-1 Glycoprotein Vaccine |
| Zdroj: | Virology. 366(2):245-262 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2007.04.033 |
| Popis: | To assess the potential of native Envelope glycoprotein (Env) trimers as neutralizing antibody vaccines, we immunized guinea pigs with three types of VLPs and soluble gp120. Particles included “SOS-VLPs” (bearing disulfide-shackled functional trimers), “UNC-VLPs” (bearing uncleaved nonfunctional Env) and “naked VLPs” (bearing no Env). The SOS-VLPs were found to have a density of about 27 native trimers per particle, approximately twice that of live inactivated HIV-1 preparations. As immunogens, UNC- and SOS-VLP rapidly elicited anti-gp120 antibodies focused on the V3 loop and the gp120 coreceptor binding site. Reactivity to the gp41 immunodominant domain was absent in SOS-VLP sera, presumably because gp120–gp41 association is stabilized, effectively covering this epitope. Gp120-immune sera reacted with the receptor binding sites of gp120 and were less focused on the V3 loop. Some Env-VLP sera neutralized primary isolates at modest titers. The measurement of neutralization was found to be affected by the cell lines used. Depending on the assay particulars, non-Env specific antibodies in VLP sera could enhance infection, or nonspecifically neutralize. However, a neutralization assay using TZM-BL cells was essentially clear of these effects. We also describe a native trimer binding assay to confirm neutralization activity in a manner that completely eliminates nonspecific effects. Overall, our data suggests that Env-VLP sera were primarily focused on nonfunctional forms of Env on VLP surfaces, possibly gp120/gp41 monomers and not the trimers. Therefore, to make progress toward a more effective VLP-based vaccine, we will need to find ways to refocus the attention of B cells on native trimers. |
| Databáze: | OpenAIRE |
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