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

Dora Buzas; Adrian h Bunzel; Oskar Staufer; Emily j Milodowski; Grace l Edmunds; Joshua C Bufton; Beatriz V Vidana mateo; Sathish K N Yadav; Kapil Gupta; Charlotte Fletcher; Maia K Williamson; Alexandra Harrison; Ufuk Borucu; Julien Capin; Ore Francis; Georgia Balchin; Sophie Hall; Mirella V Vega; Fabien Durbesson; Srikanth Lingappa; Renaud Vincentelli; Joe Roe; Linda Wooldridge; Rachel Burt; Ross j l Anderson; Adrian j Mulholland; West Midlands Paediatric High Dependency Bristol uncover group; Jonathan Hare; Mick Bailey; Andrew d Davidson; Adam Finn; David Morgan; Jamie Mann; Joachim Spatz; Frederic Garzoni; Christiane Schaffitzel; Imre Berger

doi:10.1093/abt/tbad024

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

Dora Buzas, Adrian h Bunzel, Oskar Staufer, Emily j Milodowski, Grace l Edmunds, Joshua C Bufton, Beatriz V Vidana mateo, Sathish K N Yadav, Kapil Gupta, Charlotte Fletcher, Maia K Williamson, Alexandra Harrison, Ufuk Borucu, Julien Capin, Ore Francis, Georgia Balchin, Sophie Hall, Mirella V Vega, Fabien Durbesson, Srikanth LingappaRenaud Vincentelli, Joe Roe, Linda Wooldridge, Rachel Burt, Ross j l Anderson, Adrian j Mulholland, West Midlands Paediatric High Dependency Bristol uncover group, Jonathan Hare, Mick Bailey, Andrew d Davidson, Adam Finn, David Morgan, Jamie Mann, Joachim Spatz, Frederic Garzoni^*, Christiane Schaffitzel^*, Imre Berger^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	277-297
Journal	Antibody Therapeutics
Volume	6
Issue number	4
Early online date	17 Oct 2023
DOIs	https://doi.org/10.1093/abt/tbad024
Publication status	Published - 17 Oct 2023

Research Groups and Themes

Bristol BioDesign Institute
Max Planck Bristol

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/abt/tbad024Licence: CC BY

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PREDACTED: Predictive simulation for Enzyme Dynamics, Antimicrobial resistance, Catalysis and Thermoadaptation for Evolution and Design
Mulholland, A. J. (Principal Investigator)
1/08/21 → 31/07/26
Project: Research, Parent

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility

Cite this

Buzas, D., Bunzel, A. H., Staufer, O., Milodowski, E. J., Edmunds, G. L., Bufton, J. C., Vidana mateo, B. V., Yadav, S. K. N., Gupta, K., Fletcher, C., Williamson, M. K., Harrison, A., Borucu, U., Capin, J., Francis, O., Balchin, G., Hall, S., Vega, M. V., Durbesson, F., ... Berger, I. (2023). In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2. Antibody Therapeutics, 6(4), 277-297. https://doi.org/10.1093/abt/tbad024

@article{7f43378068d14beabe1ad42f4a04ca30,

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

abstract = "BackgroundDue to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens.MethodsHere, 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).ResultsOur 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.ConclusionOur 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.",

author = "Dora Buzas and Bunzel, {Adrian h} and Oskar Staufer and Milodowski, {Emily j} and Edmunds, {Grace l} and Bufton, {Joshua C} and {Vidana mateo}, {Beatriz V} and Yadav, {Sathish K N} and Kapil Gupta and Charlotte Fletcher and Williamson, {Maia K} and Alexandra Harrison and Ufuk Borucu and Julien Capin and Ore Francis and Georgia Balchin and Sophie Hall and Vega, {Mirella V} and Fabien Durbesson and Srikanth Lingappa and Renaud Vincentelli and Joe Roe and Linda Wooldridge and Rachel Burt and Anderson, {Ross j l} and Mulholland, {Adrian j} and {Bristol uncover group}, {West Midlands Paediatric High Dependency} and Jonathan Hare and Mick Bailey and Davidson, {Andrew d} and Adam Finn and David Morgan and Jamie Mann and Joachim Spatz and Frederic Garzoni and Christiane Schaffitzel and Imre Berger",

year = "2023",

month = oct,

day = "17",

doi = "10.1093/abt/tbad024",

language = "English",

volume = "6",

pages = "277--297",

journal = "Antibody Therapeutics",

issn = "2516-4236",

publisher = "Oxford University Press",

number = "4",

}

Buzas, D, Bunzel, AH, Staufer, O, Milodowski, EJ , Edmunds, GL, Bufton, JC, Vidana mateo, BV, Yadav, SKN, Gupta, K, Fletcher, C, Williamson, MK, Harrison, A, Borucu, U, Capin, J, Francis, O, Balchin, G , Hall, S, Vega, MV, Durbesson, F, Lingappa, S, Vincentelli, R, Roe, J, Wooldridge, L, Burt, R, Anderson, RJL , Mulholland, AJ, Bristol uncover group, WMPHD, Hare, J, Bailey, M , Davidson, AD , Finn, A, Morgan, D, Mann, J, Spatz, J, Garzoni, F, Schaffitzel, C & Berger, I 2023, 'In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2', Antibody Therapeutics, vol. 6, no. 4, pp. 277-297. https://doi.org/10.1093/abt/tbad024

TY - JOUR

T1 - In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2

AU - Buzas, Dora

AU - Bunzel, Adrian h

AU - Staufer, Oskar

AU - Milodowski, Emily j

AU - Edmunds, Grace l

AU - Bufton, Joshua C

AU - Vidana mateo, Beatriz V

AU - Yadav, Sathish K N

AU - Gupta, Kapil

AU - Fletcher, Charlotte

AU - Williamson, Maia K

AU - Harrison, Alexandra

AU - Borucu, Ufuk

AU - Capin, Julien

AU - Francis, Ore

AU - Balchin, Georgia

AU - Hall, Sophie

AU - Vega, Mirella V

AU - Durbesson, Fabien

AU - Lingappa, Srikanth

AU - Vincentelli, Renaud

AU - Roe, Joe

AU - Wooldridge, Linda

AU - Burt, Rachel

AU - Anderson, Ross j l

AU - Mulholland, Adrian j

AU - Bristol uncover group, West Midlands Paediatric High Dependency

AU - Hare, Jonathan

AU - Bailey, Mick

AU - Davidson, Andrew d

AU - Finn, Adam

AU - Morgan, David

AU - Mann, Jamie

AU - Spatz, Joachim

AU - Garzoni, Frederic

AU - Schaffitzel, Christiane

AU - Berger, Imre

PY - 2023/10/17

Y1 - 2023/10/17

N2 - BackgroundDue to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens.MethodsHere, 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).ResultsOur 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.ConclusionOur 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.

AB - BackgroundDue to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens.MethodsHere, 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).ResultsOur 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.ConclusionOur 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.

U2 - 10.1093/abt/tbad024

DO - 10.1093/abt/tbad024

M3 - Article (Academic Journal)

C2 - 38075238

SN - 2516-4236

VL - 6

SP - 277

EP - 297

JO - Antibody Therapeutics

JF - Antibody Therapeutics

IS - 4

ER -

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

Abstract

Research Groups and Themes

UN SDGs

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Projects

PREDACTED: Predictive simulation for Enzyme Dynamics, Antimicrobial resistance, Catalysis and Thermoadaptation for Evolution and Design

Equipment

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

Cite this