Covalent decoration of adenovirus vector capsids with the carbohydrate epitope αGal does not improve vector immunogenicity, but allows to study the in vivo fate of adenovirus immunocomplexes

PLoS One. 2017 May 4;12(5):e0176852. doi: 10.1371/journal.pone.0176852. eCollection 2017.

Abstract

Adenovirus-based vectors are promising tools for genetic vaccination. However, several obstacles have to be overcome prior to a routine clinical application of adenovirus-based vectors as efficacious vectored vaccines. The linear trisaccharide epitope αGal (alpha-Gal) with the carbohydrate sequence galactose-α-1,3-galactosyl-β-1,4-N-acetylglucosamine has been described as a potent adjuvant for recombinant or attenuated vaccines. Humans and α-1,3-galactosyltransferase knockout mice do not express this epitope. Upon exposure of α-1,3-galactosyltransferase-deficient organisms to αGal in the environment, large amounts of circulating anti-Gal antibodies are produced consistently. Immunocomplexes formed between recombinant αGal-decorated vaccines and anti-Gal antibodies exhibit superior immunogenicity. We studied the effects of the trisaccharide epitope on CD8 T cell responses that are directed specifically to vector-encoded transgenic antigens. For that, covalently αGal-decorated adenovirus vectors were delivered to anti-Gal α-1,3-galactosyltransferase knockout mice. We generated replication-defective, E1-deleted adenovirus type 5 vectors that were decorated with αGal at the hexon hypervariable regions 1 or 5, at fiber knob, or at penton base. Surprisingly, none of the adenovirus immunocomplexes being formed from αGal-decorated adenovirus vectors and anti-Gal immunoglobulins improved the frequencies of CD8 T cell responses against the transgenic antigen ovalbumin. Humoral immunity directed to the adenovirus vector was neither increased. However, our data indicated that decoration of Ad vectors with the αGal epitope is a powerful tool to analyze the fate of adenovirus immunocomplexes in vivo.

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology
  • Animals
  • Antigen-Antibody Complex*
  • Capsid*
  • Carbohydrates / immunology*
  • Cell Line
  • Female
  • Genetic Vectors*
  • Male
  • Mice
  • Mice, Knockout

Substances

  • Antigen-Antibody Complex
  • Carbohydrates

Grants and funding

Support was provided by BMBF Go-Bio grant #0315562, International Graduate School in Molecular Medicine Ulm (IGradU) (IGradU, and Excellence Initiative of the German Federal and State Governments). Additionally, the work was supported by ZBAF/Center for Biomedical Research and Education (to FK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.