| First Author | Kratzer RF | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 5 | Pages | e0176852 |
| PubMed ID | 28472163 | Mgi Jnum | J:248425 |
| Mgi Id | MGI:5919652 | Doi | 10.1371/journal.pone.0176852 |
| Citation | Kratzer RF, et al. (2017) Covalent decoration of adenovirus vector capsids with the carbohydrate epitope alphaGal does not improve vector immunogenicity, but allows to study the in vivo fate of adenovirus immunocomplexes. PLoS One 12(5):e0176852 |
| abstractText | 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 alphaGal (alpha-Gal) with the carbohydrate sequence galactose-alpha-1,3-galactosyl-beta-1,4-N-acetylglucosamine has been described as a potent adjuvant for recombinant or attenuated vaccines. Humans and alpha-1,3-galactosyltransferase knockout mice do not express this epitope. Upon exposure of alpha-1,3-galactosyltransferase-deficient organisms to alphaGal in the environment, large amounts of circulating anti-Gal antibodies are produced consistently. Immunocomplexes formed between recombinant alphaGal-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 alphaGal-decorated adenovirus vectors were delivered to anti-Gal alpha-1,3-galactosyltransferase knockout mice. We generated replication-defective, E1-deleted adenovirus type 5 vectors that were decorated with alphaGal at the hexon hypervariable regions 1 or 5, at fiber knob, or at penton base. Surprisingly, none of the adenovirus immunocomplexes being formed from alphaGal-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 alphaGal epitope is a powerful tool to analyze the fate of adenovirus immunocomplexes in vivo. |
