Kinase-deficient CMVpp65 triggers a CMVpp65 specific T-cell immune response in HLA-A*0201.Kb transgenic mice after DNA immunization

Scand J Immunol. 2002 Jun;55(6):592-8. doi: 10.1046/j.1365-3083.2002.01099.x.

Abstract

CMVpp65, a candidate component of human cytomegalovirus (CMV) vaccines, has phosphokinase (PK) activity that could affect vaccine safety. A mutated form of CMVpp65 substituting asparagine for lysine at the adenosine triphosphate (ATP)-binding site (CMVpp65mII) is kinase-deficient. Using DNA immunizations in a transgenic human leucocyte antigen (HLA)A*0201.Kb mouse model, the mutated CMVpp65 induced cytotoxic T lymphocytes (CTL) immunity similarly to native CMVpp65. Murine CTL lines generated from these immunizations killed human cells either after sensitization with CMVpp65-specific peptides or after infection with either CMV-Towne strain or rvac-pp65. It is proposed that CMVpp65mII be evaluated in candidate vaccines for CMV.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / prevention & control
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • HLA-A Antigens / immunology*
  • Humans
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Phosphoproteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccinia virus / genetics
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*
  • Viral Matrix Proteins / metabolism

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Phosphoproteins
  • Vaccines, DNA
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa