CoroNAb

In early 2020, together with colleagues at our department and internationally, we formed the CoroNAb consortium with the aim to develop neutralising antibodies against the then recently emerged novel coronavirus, subsequently named SARS-CoV-2. Our work expanded as the pandemic did, and can be summarised under the headings below.












Left, virion image generously supplied by scientific illustrator Mattias Karlén. Centre, Tyson the alpaca, pictured on pasture at Preclinics. Right, Ainhoa setting up infectious virus neutralisation assay in the Biomedicum BSL3 laboratory and featured on TV4 news. 


Camelid-derived single-chain antibodies (nanobodies)

Leo Hanke, Laura Vidakovics Perez, Daniel J. Sheward, Hrishikesh Das, Tim Schulte, Ainhoa Moliner-Morro, Martin Corcoran, Adnane Achour, Gunilla B. Karlsson Hedestam, B. Martin Hällberg, Ben Murrell and Gerald M. McInerney (2020) An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction. Nature Communications, 11(1):4420


In this work, we developed an alpaca-derived single-chain only antibody fragment (nanobody) which binds to the spike protein of SARS-CoV-2 and blocks its interaction with the cellular receptor ACE2.

Left, three Ty1 nanobody molecules (grey) shown in complex with three receptor-binding domains of the trimeric SARS-CoV-2 spike glycoprotein molecule (monomers in yellow, magenta and green). Structure solved using cryo-EM by Martin Hällberg and Hrishikesh Das (CMB, KI).




Tânia F. Custódio, Hrishikesh Das, Daniel J Sheward, Leo Hanke, Samuel Pazicky, Joanna Pieprzyk, Michèle Sorgenfrei, Martin Schroer, Andrey Gruzinov, Cy Jeffries, Melissa Graewert, Dmitri Svergun, Nikolay Dobrev, Kim Remans, Markus A. Seeger, Gerald M McInerney, Benjamin Murrell, Martin Hällberg and Christian Löw (2020) Selection and structural analysis of sybodies neutralizing SARS-CoV-2. Nature Communications, 11(1):5588


Leo Hanke*, Hrishikesh Das*, Daniel J. Sheward, Laura Vidakovics Perez, Egon Urgard, Ainhoa Moliner-Morro, Vivien Karl, Alec Pankow, Changil Kim, Natalie L Smith, Bartlomiej Porebski, Oscar Fernandez-Capetillo, Erdinc Sezgin, Gabriel K Pedersen, Jonathan Coquet, B. Martin Hällberg, Ben Murrell# and Gerald M. McInerney# (2022) A bispecific monomeric nanobody induces spike trimer dimers and suppresses SARS-CoV-2 in vivo. Nature Communications, 13: 155. *,# equal contribution.



Left, Two SARS-CoV-2 spike glycoprotein trimers in a head-to-head conformation with 6 molecules of Fu2 nanobody (red) interpolated between them. Structure solved using cryo-EM by Martin Hällberg and Hrishikesh Das (CMB, KI).


Leo Hanke*, Daniel J. Sheward*, Alec Pankow, Laura Perez Vidakovics, Vivien Karl, Changil Kim, Egon Urgard, Natalie L. Smith,

Juan Astorga-Wells, Simon Ekström, Jonathan Coquet, Gerald M. McInerney# and Ben Murrell# (2022) Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralising SARS-CoV-2 nanobodies. Science Advances, Accepted for publication. *,# equal contribution
bioRxiv version here.


Serology

Niclas Roxhed, Annika Bendes, Matilda Dale, Cecilia Mattsson, Leo Hanke, Tea Dodig-Crnkovic, Birthe Meineke, Simon Elsässer, Juni Andréll, Sebastian Havervall, Charlotte Thålin, Carina Eklund, Joakim Dillner, Mun-Gwan Hong, Cecilia E Thomas, Olof Beck, Gerald McInerney, Benjamin Murrell, Claudia Fredolini and Jochen M Schwenk (2021) A translational and multiplexed serology approach to determine the prevalence of anti-SARS-CoV-2 antibodies in home-sampled blood. Nature Communications, 12(1):3695.


Xaquin Castro Dopico, Sandra Muschiol, Murray Christian, Leo Hanke, Daniel J. Sheward, Nastasiya F. Grinberg, Joanna Rorbach, Gordana Bogdanovic, Gerald M. McInerney, Tobias Allander, Chris Wallace, Ben Murrell, Jan Albert, Gunilla B. Karlsson Hedestam (2021) Sero-positivity in blood donors and pregnant women during the first 12 months of SARS-CoV-2 transmission in Stockholm, Sweden. J Internal Medicine, doi:10.1111/joim.13304.


Vaccinology

Daniel J Sheward, Marco Mandolesi, Changil Kim, Leo Hanke, Laura Perez Vidakovics, Gerald McInerney, Gunilla Karlsson Hedestam, Ben Murrell (2021) Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models. Cell Reports Medicine, 16;2(11):100450.


Marco Mandolesi, Daniel J Sheward, Leo Hanke, Junjie Ma, Pradeepa Pushparaj, Laura Perez Vidakovics, Kim Chang Il, Karin Loré, Xaquin Castro Dopico, Jonathan Coquet, Gerald McInerney, Gunilla Karlsson Hedestam, Ben Murrell (2021) SARS-CoV-2 protein subunit vaccines reproducibly elicit potent neutralizing antibody responses. Cell Reports Medicine 2:100252.


Inga Szurgot, Leo Hanke, Daniel J. Sheward, Laura Perez Vidakovics, Ben Murrell, Gerald M. McInerney and Peter Liljeström (2021) DNA-launched RNA Replicon Vaccines Induce Potent anti-SARS-CoV-2 Immune Responses in mice. Scientific Reports 11:3125.


K. Wørzner, D. Sheward, S. Tandrup Schmidt, L. Hanke, J. Zimmermann, G. McInerney, G. B. Karlsson Hedestam, B. Murrell, D. Christensen and G. K. Pedersen (2021) Adjuvanted SARS-CoV-2 spike protein facilitates neutralizing antibodies and CD4 T cell responses after a single immunization in mice. EBioMedicine 63:103197


Nanotechnology

Padryk Merkl*, Siwen Long*, Gerald M. McInerney#, and Georgios A. Sotiriou# (2021) Antiviral activity of silver, copper oxide and zinc oxide nanoparticle coatings against SARS-CoV-2. Nanomaterials, 17;11(5):1312
*,# equal contribution


Atefeh Khorsand Kheirabad, Xuefeng Pan, Siwen Long, Zdravko Kochovski, Yan Lu, Gerald McInerney, Jiayin Yuan (2021) Colloidal dispersion of poly(ionic liquid)/Cu composite particles for protective surface coating against SARS-CoV-2. Nano Select doi.org/10.1002/nano.202100069.