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TitleModular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.
Journal, issue, pagesMol Ther, Vol. 30, Issue 12, Page 3639-3657, Year 2022
Publish dateDec 7, 2022
AuthorsMatthew D J Dicks / Louisa M Rose / Rebecca A Russell / Lesley A H Bowman / Carl Graham / Jose M Jimenez-Guardeño / Katie J Doores / Michael H Malim / Simon J Draper / Mark Howarth / Sumi Biswas /
PubMed AbstractAdenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine- ...Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.
External linksMol Ther / PubMed:35949171 / PubMed Central
MethodsEM (single particle)
Resolution10.5 Å
Structure data

EMDB-14370: Ad-DogTag:DogCatcher-RBD
Method: EM (single particle) / Resolution: 10.5 Å

EMDB-14371: Ad-DogTag
Method: EM (single particle) / Resolution: 10.5 Å

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