Viruses, Vol. 12, Pages 242: Measles Vaccines Designed for Enhanced CD8+ T Cell Activation

Viruses, Vol. 12, Pages 242: Measles Vaccines Designed for Enhanced CD8+ T Cell Activation Viruses doi: 10.3390/v12020242 Authors: Busch Kubon Mayer Pidelaserra-Martí Albert Hoyler Heidbuechel Stephenson Lichty Osen Eichmüller Jäger Ungerechts Engeland Priming and activation of CD8+ T cell responses is crucial to achieve anti-viral and anti-tumor immunity. Live attenuated measles vaccine strains have been used successfully for immunization for decades and are currently investigated in trials of oncolytic virotherapy. The available reverse genetics systems allow for insertion of additional genes, including heterologous antigens. Here, we designed recombinant measles vaccine vectors for priming and activation of antigen-specific CD8+ T cells. For proof-of-concept, we used cytotoxic T lymphocyte (CTL) lines specific for the melanoma-associated differentiation antigen tyrosinase-related protein-2 (TRP-2), or the model antigen chicken ovalbumin (OVA), respectively. We generated recombinant measles vaccine vectors with TRP-2 and OVA epitope cassette variants for expression of the full-length antigen or the respective immunodominant CD8+ epitope, with additional variants mediating secretion or proteasomal degradation of the epitope. We show that these recombinant measles virus vectors mediate varying levels of MHC class I (MHC-I)-restricted epitope presentation, leading to activation of cognate CTLs, as indicated by secretion of int...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research