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Glycoconj J. 2021 Aug;38(4):437-446. doi: 10.1007/s10719-021-09999-3. Epub 2021 Apr 14.

On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines.

Glycoconjugate journal

Maruthi Prasanna, Malgorzata Podsiadla-Bialoskorska, Damian Mielecki, Nicolas Ruffier, Amina Fateh, Annie Lambert, Mathieu Fanuel, Emilie Camberlein, Ewa Szolajska, Cyrille Grandjean

Affiliations

  1. Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, CNRS, UMR 6286, F-44000, Nantes, France.
  2. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106, Warszawa, Poland.
  3. UR BIA, INRAE, F-44316, Nantes, France.
  4. BIBS facility, INRAE, F-44316, Nantes, France.
  5. Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, CNRS, UMR 6286, F-44000, Nantes, France. [email protected].

PMID: 33852106 DOI: 10.1007/s10719-021-09999-3

Abstract

Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually peptides incorporated within the protein sequences which compose the VLPs or conjugated to them. We herein described the conjugation of a synthetic tetrasaccharide mimicking the Streptococcus pneumoniae serotype 14 capsular polysaccharide to recombinant adenoviral type 3 dodecahedron, formed by the self-assembling of twelve penton bases and investigated the induced immune response when administered subcutaneously (s.c.). Whether formulated in the form of a dodecahedron or disassembled, the glycoconjugate induced an anti-protein response after two and three immunizations equivalent to that observed when the native dodecahedron was administered. On the other hand, the glycoconjugate induced a weak anti-IgM response which diminishes after two doses but no IgM-to-IgG switch was observed in mice against the serotype 14 capsular polysaccharide. In definitive, the whole conjugation process preserved both particulate nature and immunogenicity of the adenoviral dodecahedron. Further studies are needed to fully exploit adenoviral dodecahedron potential in terms of plasticity towards sequence engineering and of its capacity to stimulate the immune system via the intranasal route of administration as well as to shift the response to the carbohydrate antigen by playing both with the carbohydrate to protein ratio and the length of the synthetic carbohydrate antigen.

Keywords: Adenovirus dodecahedron; Carbohydrate antigen; Glycoconjugate vaccine; Streptococcus pneumoniae; Virus-like particle

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