Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses

Immunity. 2021 Apr 13;54(4):769-780.e6. doi: 10.1016/j.immuni.2021.03.004. Epub 2021 Apr 5.


An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV.

Keywords: RSV; antibody repertoire; cryo-EM structure; fusion glycoprotein; memory B cells; neutralizing antibodies; prefusion; public clonotypes; respiratory syncytial virus.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Antibody Formation / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Cohort Studies
  • Epitopes / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / immunology*
  • Vaccination / methods
  • Viral Fusion Proteins / immunology
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Respiratory Syncytial Virus Vaccines
  • Viral Fusion Proteins