Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus

Cell. 2019 Mar 7;176(6):1420-1431.e17. doi: 10.1016/j.cell.2019.01.046.


Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.

Keywords: computational protein design; nanoparticles; neutralizing antibodies; respiratory syncytial virus; self-assembly; vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Viral / immunology
  • Caveolin 1
  • Cell Line
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / therapeutic use
  • Primary Cell Culture
  • Respiratory Syncytial Viruses / immunology*
  • Respiratory Syncytial Viruses / pathogenicity
  • Vaccination / methods*
  • Vaccines / immunology
  • Viral Fusion Proteins / immunology
  • Viral Fusion Proteins / metabolism
  • Viral Fusion Proteins / physiology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • CAV1 protein, human
  • Caveolin 1
  • F protein, human respiratory syncytial virus
  • Vaccines
  • Viral Fusion Proteins