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Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform

Abstract : Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity.
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Pré-publication, Document de travail
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https://hal.archives-ouvertes.fr/hal-03409188
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Soumis le : vendredi 29 octobre 2021 - 15:08:12
Dernière modification le : mercredi 10 novembre 2021 - 03:22:46

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Christopher Chevillard, Axelle Amen, S Besson, D Hannani, Isabelle Bally, et al.. Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform. 2021. ⟨hal-03409188⟩

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