Cellular immunogenicity of novel gene immunogens in mice monitored by in vivo imaging

Elizaveta Starodubova, Olga Krotova, David Hallengärd, Yulia Kuzmenko, Gunnel Engström, Diana Legzdina, Oleg Latyshev, Olesja Eliseeva, Anna Karin Maltais, Vera Tunitskaya, Vadim Karpov, Andreas Bråve, Maria Isaguliants (Corresponding Author)

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The efficient cell-mediated immune response clears cells expressing deoxyribonucleic acid (DNA) immunogens, but there are no methods to monitor this in vivo. We hypothesized that immune-mediated clearance can be monitored in vivo if DNA immunogens are coexpressed with reporter(s). To test this, we designed genes encoding human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) fused via its N-or C-terminus to 30-amino acid-long Gly-Ala-repeat of Epstein-Barr virus nuclear antigen 1 or via the N-terminus to the transport signal of invariant chain/Ii or inserted between the cytoplasmic and luminal domains of lysosomeassociated membrane protein I (LAMP). DNA immunogens mixed with luciferase gene were injected into BALB/c mice with subsequent electroporation. Reporter expression seen as luminescence was monitored by in vivo imaging. When luminescence faded, mice were sacrificed, and their splenocytes were stimulated with RT-derived antigens. Fading of luminescence correlated with the RT-specific secretion of interferon-c and interleukin-2. Both immune and in vivo imaging techniques concordantly demonstrated an enhanced immunogenicity of RT-LAMP and of the N-terminal Gly-Ala-RT fusion genes. In vivo imaging performed as an animalsparing method to estimate the overall performance of DNA immunogens, predicting it early in the experiment. So far, in vivo imaging cannot be a substitute for conventional immune assays, but it is supplementary to them. Further experiments are needed to identify which arms of cellular immune response in vivo imaging monitors best.

Original languageEnglish
Pages (from-to)471-486
Number of pages16
JournalMolecular Imaging
Volume11
Issue number6
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

Field of Science*

  • 3.4 Medical biotechnology
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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