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

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 ?Gal (alpha-Gal) with the carbohydrate sequence galactose-?-1,3-galactosyl-?-1,4-N-acetylglucosamine has been described as a potent adjuvant for recombinant or attenuated vaccines. Humans and ?-1,3-galactosyltransferase knockout mice do not express this epitope. Upon exposure of ?-1,3-galactosyltransferase-deficient organisms to ?Gal in the environment, large amounts of circulating anti-Gal antibodies are produced consistently. Immunocomplexes formed between recombinant ?Gal-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 ?Gal-decorated adenovirus vectors were delivered to anti-Gal ?-1,3-galactosyltransferase knockout mice. We generated replication-defective, E1-deleted adenovirus type 5 vectors that were decorated with ?Gal at the hexon hypervariable regions 1 or 5, at fiber knob, or at penton base. Surprisingly, none of the adenovirus immunocomplexes being formed from ?Gal-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 ?Gal epitope is a powerful tool to analyze the fate of adenovirus immunocomplexes in vivo.

SUBMITTER: Kratzer RF 

PROVIDER: S-EPMC5417563 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature