Recombinant LCMV Vectors Induce Protective Immunity Following Homologous and Heterologous Vaccinations

Mol Ther. 2017 Nov 1;25(11):2533-2545. doi: 10.1016/j.ymthe.2017.07.012. Epub 2017 Jul 20.

Abstract

Successful vaccination against cancer and infectious diseases relies on the induction of adaptive immune responses that induce high-titer antibodies or potent cytoxic T cell responses. In contrast to humoral vaccines, the amplification of cellular immune responses is often hampered by anti-vector immunity that either pre-exists or develops after repeated homologous vaccination. Replication-defective lymphocytic choriomeningitis virus (LCMV) vectors represent a novel generation of vaccination vectors that induce potent immune responses while escaping recognition by neutralizing antibodies. Here, we characterize the CD8 T cell immune response induced by replication-defective recombinant LCMV (rLCMV) vectors with regard to expansion kinetics, trafficking, phenotype, and function and we perform head-to-head comparisons of the novel rLCMV vectors with established vectors derived from adenovirus, vaccinia virus, or Listeria monocytogenes. Our results demonstrate that replication-deficient rLCMV vectors are safe and ideally suited for both homologous and heterologous vaccination regimens to achieve optimal amplification of CD8 T cell immune responses in vivo.

Keywords: CD8 T cells; lymphocytic choriomeningitis virus; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Adoptive Transfer
  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Gene Expression
  • Genes, Reporter
  • Genetic Vectors / chemistry
  • Genetic Vectors / immunology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / immunology
  • Immunity, Cellular*
  • Immunologic Memory
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology
  • Lymphocytic choriomeningitis virus / genetics
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / transplantation
  • Vaccination / methods*
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology

Substances

  • Antigens, Viral
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Ovalbumin