[PDF][PDF] High-density array of well-ordered HIV-1 spikes on synthetic liposomal nanoparticles efficiently activate B cells

J Ingale, A Stano, J Guenaga, SK Sharma, D Nemazee… - Cell reports, 2016 - cell.com
J Ingale, A Stano, J Guenaga, SK Sharma, D Nemazee, MB Zwick, RT Wyatt
Cell reports, 2016cell.com
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 …
Summary
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.
cell.com