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Title generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2.
Journal, issue, pagesAntib Ther, Vol. 6, Issue 4, Page 277-297, Year 2023
Publish dateOct 17, 2023
AuthorsDora 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 / Bristol Uncover Group / Jonathan Hare / Mick Bailey / Andrew D Davidson / Adam Finn / David Morgan / Jamie Mann / Joachim Spatz / Frederic Garzoni / Christiane Schaffitzel / Imre Berger /
PubMed AbstractBACKGROUND: 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 ...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 antibody selection and 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). 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 EC. 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.
External linksAntib Ther / PubMed:38075238 / PubMed Central
MethodsEM (single particle)
Resolution2.36 - 4.06 Å
Structure data

16512

8c9n

EMDB-16512, PDB-8c9n:
MiniCoV-ADDomer, a SARS-CoV-2 epitope presenting viral like particle
Method: EM (single particle) / Resolution: 2.36 Å

EMDB-16522: Structure of ADDoCoV-ADAH11
Method: EM (single particle) / Resolution: 4.06 Å

Source
  • human adenovirus b3
  • Lama glama (llama)
KeywordsVIRUS LIKE PARTICLE / ADDomer / VLP / Viral / like / Particle / AD3 / Penton / base / vaccine / COVID-19 / COVID / MINI-COVID / Dodecahedron / pb / protein / adenovirus / human

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