High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells

Cell Rep. 2016 May 31;15(9):1986-99. doi: 10.1016/j.celrep.2016.04.078. Epub 2016 May 19.


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.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • B-Lymphocytes / immunology*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • HIV Antibodies / immunology
  • HIV-1 / metabolism*
  • Interferometry
  • Liposomes / chemistry*
  • Liposomes / ultrastructure
  • Lymphocyte Activation / immunology*
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Protein Multimerization
  • Rabbits
  • Solubility
  • Temperature
  • env Gene Products, Human Immunodeficiency Virus / chemistry*


  • Antibodies, Neutralizing
  • HIV Antibodies
  • Liposomes
  • env Gene Products, Human Immunodeficiency Virus