Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients

J Infect Dis. 2019 Jun 19;220(2):228-232. doi: 10.1093/infdis/jiz089.

Abstract

A human cytomegalovirus (HCMV) vaccine is urgently needed to protect against primary infection and enhance existing immunity in HCMV-infected individuals (HCMV+). Using sera from HCMV+ glycoprotein B/MF59 vaccine recipients prior to transplant, we investigated the composition of the immune response. Vaccination boosted preexisting humoral responses in our HCMV+ cohort but did not promote de novo responses against novel linear epitopes. This suggests that prior natural infection has a profound effect on shaping the antibody repertoire and subsequent response to vaccination ("original antigenic sin"). Thus, vaccination of HCMV+ may require strategies of epitope presentation distinct from those intended to prevent primary infection.

Keywords: antibody responses; cytomegalovirus; original antigenic sin; vaccination.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Cytomegalovirus Vaccines / immunology*
  • Double-Blind Method
  • Epitopes / immunology
  • Humans
  • Polysorbates
  • Squalene / immunology*
  • Vaccination / methods
  • Viral Envelope Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytomegalovirus Vaccines
  • Epitopes
  • MF59 oil emulsion
  • Polysorbates
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • Squalene