Sequence space localization in the immune system response to vaccination and disease

Phys Rev Lett. 2003 Aug 8;91(6):068101. doi: 10.1103/PhysRevLett.91.068101. Epub 2003 Aug 7.


We introduce a model of protein evolution to explain limitations in the immune system response to vaccination and disease. The phenomenon of original antigenic sin, wherein vaccination creates memory sequences that can increase susceptibility to future exposures to the same disease, is explained as stemming from localization of the immune system response in antibody sequence space. This localization is a result of the roughness in sequence space of the evolved antibody affinity constant for antigen and is observed for diseases with high year-to-year mutation rates, such as influenza.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / immunology*
  • Antigens / genetics
  • Antigens / immunology*
  • B-Lymphocytes / immunology
  • Evolution, Molecular
  • Humans
  • Immunologic Memory
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Kinetics
  • Models, Immunological*
  • Orthomyxoviridae / immunology
  • Thermodynamics
  • Viral Proteins / immunology


  • Antibodies
  • Antigens
  • Influenza Vaccines
  • Viral Proteins