Scientific Publications
- PMID: 27210756
- Title: High Density Array of Well Ordered HIV 1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells
- Abstract: A major step toward an HIV-1 vaccine is an immunogen capable of inducing neutralizing antibodies. Envelope glycoprotein (Env) mimetics, such as the NFL and SOSIP designs, generate native-like, well-ordered trimers and elicit tier 2 homologous neutralization (SOSIPs). We reasoned that the display of well-ordered trimers by high-density, particulate array would increase B cell activation compared to soluble trimers. Here, we present the design of liposomal nanoparticles displaying well-ordered Env spike trimers on their surface. Biophysical analysis, cryo- and negative stain electron microscopy, as well as binding analysis with a panel of broadly neutralizing antibodies confirm a high-density, well-ordered trimer particulate array. The Env-trimer-conjugated liposomes were superior to soluble trimers in activating B cells ex vivo and germinal center B cells in vivo. In addition, the trimer-conjugated liposomes elicited modest tier 2 homologous neutralizing antibodies. The trimer-conjugated liposomes represent a promising initial lead toward the development of more effective HIV vaccine immunogens.
- Date: 1970-08-22
- Year: 2017
- Journal: Cell Rep
- PMID Author: Ingale J, Stano A, Guenaga J, Sharma SK, Nemazee D, Zwick MB, Wyatt RT
- PMC Link #: PMC4889521
High Density Array of Well Ordered HIV 1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells
High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells. Cell Rep 2016;15(9):1986-99 doi: 10.1016/j.celrep.2016.04.078
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