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Journal Articles Antibody Therapeutics Year : 2023

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2

Dora Buzas
  • Function : Author
Adrian Bunzel
  • Function : Author
Oskar Staufer
  • Function : Author
Emily Milodowski
  • Function : Author
Grace Edmunds
  • Function : Author
Joshua Bufton
  • Function : Author
Beatriz Vidana Mateo
  • Function : Author
Sathish Yadav
  • Function : Author
Kapil Gupta
  • Function : Author
Charlotte Fletcher
  • Function : Author
Maia Williamson
  • Function : Author
Alexandra Harrison
  • Function : Author
Ufuk Borucu
  • Function : Author
Julien Capin
  • Function : Author
Ore Francis
  • Function : Author
Georgia Balchin
  • Function : Author
Sophie Hall
  • Function : Author
Mirella Vega
  • Function : Author
Fabien Durbesson
  • Function : Author
Srikanth Lingappa
  • Function : Author
Joe Roe
  • Function : Author
Linda Wooldridge
  • Function : Author
Rachel Burt
  • Function : Author
Ross Anderson
  • Function : Author
Adrian Mulholland
  • Function : Author
Jonathan Hare
  • Function : Author
Mick Bailey
  • Function : Author
Andrew Davidson
  • Function : Author
Adam Finn
  • Function : Author
David Morgan
  • Function : Author
Jamie Mann
  • Function : Author
Joachim Spatz
  • Function : Author
Frederic Garzoni
  • Function : Author
Christiane Schaffitzel
  • Function : Author
Imre Berger

Abstract

Abstract Background Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens. Methods Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection and in vivo immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). In vitro generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron. Conclusion Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.

Dates and versions

hal-04382381 , version 1 (09-01-2024)

Identifiers

Cite

Dora Buzas, Adrian Bunzel, Oskar Staufer, Emily Milodowski, Grace Edmunds, et al.. In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2. Antibody Therapeutics, 2023, 6 (4), pp.277-297. ⟨10.1093/abt/tbad024⟩. ⟨hal-04382381⟩
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