Serum antibody response to the gH/gL/pUL128-131 five-protein complex of human cytomegalovirus (HCMV) in primary and reactivated HCMV infections

J Clin Virol. 2011 Oct;52(2):113-8. doi: 10.1016/j.jcv.2011.06.018. Epub 2011 Aug 4.

Abstract

Background: Recently, a new human cytomegalovirus (HCMV) glycoprotein complex has been identified and potentially proposed as a vaccine.

Objective: The aim of this study was to determine whether the HCMV gH/gL/pUL128-pUL130-pUL131 (gH/gL/pUL128-131) 5-protein (pentameric) complex (which has been recently found to be indispensable for the infection of endothelial and epithelial cells) is able to elicit a consistent antibody response in both primary and reactivated HCMV infections.

Study design: The antibody response was determined by both indirect immunofluorescence (IFA) and ELISA, using fixed (IFA) or lysed (ELISA) epithelial (ARPE-19) cells infected with one or more adenoviral vectors, each carrying one HCMV gene and, in parallel, with a control adenovirus vector.

Results: The specificity of results was determined by the reactivity of human neutralizing mAbs recognizing two, three, or four proteins of the complex. In 14 cases of primary infection, an IgG antibody seroconversion to the UL128-131 gene products was consistently detected within 2-4 weeks after onset of infection, while antibodies persisted for at least 12 months. The IgG antibody response to UL128-131 gene products was generally superior to the response to gH and appeared to follow the neutralizing antibody response (as determined in epithelial cells). In reactivated infections, the antibody response showed a trend reminiscent of a booster response. IgG antibodies were detected in HCMV-seropositive healthy adult controls, but not in HCMV-seronegative individuals.

Conclusions: The IgG antibody response to the pentameric complex could be a major target for the evaluation of the antibody response to a pentamer-based vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / blood*
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Gene Expression Regulation, Viral
  • Genetic Vectors / genetics
  • HEK293 Cells
  • Humans
  • Immunoglobulin G / blood
  • Membrane Glycoproteins / immunology
  • Transduction, Genetic
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Immunoglobulin G
  • Membrane Glycoproteins
  • UL115 protein, Human herpesvirus 5
  • UL128 protein, human cytomegalovirus
  • Viral Envelope Proteins
  • Viral Proteins
  • glycoprotein H, Human cytomegalovirus