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

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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.

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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

MP acknowledges doctoral fellowship from the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), under the Erasmus Mundus program, NanoFar. NR thanks the Région Pays de la Loire, International Strategy Program “NanoFar+” for a travel grant. The authors gratefully acknowledge Anthony Piticco for its technical assistance, Dorian Caudal and Aude Lafoux from platform Therassey (Nantes) for animal experiments and Dr. Jadwiga Chroboczek for helpful discussion. This work used the EM facilities at the Grenoble Instruct-ERIC Center (ISBG; UMS 3518 CNRS CEA-UGA-EMBL) with support from the French Infrastructure for Integrated Structural Biology (FRISBI; ANR-10-INSB-05-02) and GRAL, a project of the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003) within the Grenoble Partnership for Structural Biology. The IBS Electron Microscope facility is supported by the Auvergne Rhône-Alpes Region, the Fonds Feder, the Fondation pour la Recherche Médicale and GIS-IBiSA. Finally, We also thank the mass spectrometry core facility of CRNH for exact mass determination.

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Authors and Affiliations

  1. Unité Fonctionnalité et Ingénierie des Protéines (UFIP), Université de Nantes, CNRS, UMR 6286, F-44000, Nantes, France

    Maruthi Prasanna, Nicolas Ruffier, Amina Fateh, Annie Lambert, Emilie Camberlein & Cyrille Grandjean

  2. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106, Warszawa, Poland

    Malgorzata Podsiadla-Bialoskorska, Damian Mielecki, Nicolas Ruffier & Ewa Szolajska

  3. UR BIA, INRAE, F-44316, Nantes, France

    Mathieu Fanuel

  4. BIBS facility, INRAE, F-44316, Nantes, France

    Mathieu Fanuel

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  1. Maruthi Prasanna
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  2. Malgorzata Podsiadla-Bialoskorska
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Correspondence to Cyrille Grandjean.

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Prasanna, M., Podsiadla-Bialoskorska, M., Mielecki, D. et al. On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines. Glycoconj J 38, 437–446 (2021). https://doi.org/10.1007/s10719-021-09999-3

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