@article{3bb3c6fe50ff426986f2c24ba8eff5e7,
title = "Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2",
abstract = "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.",
keywords = "adenovirus, protein superglue, SARS-CoV-2, vaccine vector, vector engineering",
author = "Dicks, {Matthew D.J.} and Rose, {Louisa M.} and Russell, {Rebecca A.} and Bowman, {Lesley A.H.} and Carl Graham and Jimenez-Guarde{\~n}o, {Jose M.} and Doores, {Katie J.} and Malim, {Michael H.} and Draper, {Simon J.} and Mark Howarth and Sumi Biswas",
note = "Funding Information: The authors would like to thank Genevieve Labbe, Sophie Porret, Laura Bilb{\'e}, Jeanette Wagener, Rebecca Dabbs, and Jing Jin for helpful advice and assistance. We thank Viv Clark, Heather Chandler, Stephen Laird, Douglas Passos, and Luke Harris for animal husbandry and technical assistance. We thank Sarah Dunn, Weili Zheng, and Mandy Janssen from NanoImaging Services, San Diego, USA for cryo-EM services and helpful discussion. Work at King's College London was funded by: Fondation Dormeur, Vaduz for funding equipment to K.J.D. a Huo Family Foundation Award to M.H.M. and K.J.D. and the MRC Genotype-to-Phenotype UK National Virology Consortium (MR/W005611/1 to M.H.M. and K.J.D.). C.G. was supported by the MRC-KCL Doctoral Training Partnership in Biomedical Sciences (MR/N013700/1). Conceptualization, M.D.J.D. S.J.D. M.H. and S.B.; methodology, M.D.J.D. R.A.R. C.G. K.J.D. M.H.M. S.J.D. M.H. and S.B.; Investigation, M.D.J.D. L.M.R. R.A.R. L.A.H.B. C.G. and J.M.J.-G.; Visualization, M.D.J.D.; Resources, M.H. and J.M.J.-G.; Writing – original draft, M.D.J.D.; Writing – review & editing, M.D.J.D. M.H. and S.B. M.D.J.D. L.M.R. R.A.R. and L.A.H.B. are employees of SpyBiotech Ltd. S.B. is CSO and co-founder of SpyBiotech Ltd. S.J.D. and M.H. are co-founders of SpyBiotech Ltd, and M.H. is also an author on a number of patents relating to protein superglues, including the DogTag/DogCatcher technology. C.G. J.M.J.-G. K.J.D. and M.H.M. declare no competing interests. Funding Information: The authors would like to thank Genevieve Labbe, Sophie Porret, Laura Bilb{\'e}, Jeanette Wagener, Rebecca Dabbs, and Jing Jin for helpful advice and assistance. We thank Viv Clark, Heather Chandler, Stephen Laird, Douglas Passos, and Luke Harris for animal husbandry and technical assistance. We thank Sarah Dunn, Weili Zheng, and Mandy Janssen from NanoImaging Services, San Diego, USA for cryo-EM services and helpful discussion. Work at King{\textquoteright}s College London was funded by: Fondation Dormeur , Vaduz for funding equipment to K.J.D., a Huo Family Foundation Award to M.H.M. and K.J.D., and the MRC Genotype-to-Phenotype UK National Virology Consortium ( MR/W005611/1 to M.H.M. and K.J.D.). C.G. was supported by the MRC-KCL Doctoral Training Partnership in Biomedical Sciences ( MR/N013700/1 ). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = dec,
day = "7",
doi = "10.1016/j.ymthe.2022.08.002",
language = "English",
volume = "30",
pages = "3639--3657",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "12",
}
