Structure-Based Vaccine Antigen Design

Annu Rev Med. 2019 Jan 27:70:91-104. doi: 10.1146/annurev-med-121217-094234.


Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity. Success with RSV has motivated structure-based stabilization of other class I viral fusion proteins for use as immunogens and demonstrated the importance of structural information for developing vaccines against other viral pathogens, particularly difficult targets that have resisted prior vaccine development efforts. Solving viral surface protein structures also supports rapid vaccine antigen design and application of platform manufacturing approaches for emerging pathogens.

Keywords: X-ray crystallography; coronavirus; electron microscopy; immunization; influenza; nanoparticle display; platform technology; respiratory syncytial virus; vaccine development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Neutralizing / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Humans
  • Respiratory Syncytial Viruses / immunology*
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / pharmacology*
  • Viral Fusion Proteins / immunology*
  • Viral Vaccines / pharmacology*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Vaccines, Synthetic
  • Viral Fusion Proteins
  • Viral Vaccines