Nanobodies and antibodies against 2019-nCoV

Deliverables

Websites, patent fillings, videos etc. (8)

CoroNAb website for dissemination of results, and for fostering broader protocol, reagent, and result sharing by the scientific community

​CoroNAb website for dissemination of results, and for fostering broader protocol, reagent, and result sharing by the scientific community.

Formulation characteristics and physicochemical evaluation of antigen-adjuvant combinations

Formulation characteristics and physicochemical evaluation of antigen-adjuvant combinations.

Shared plasmid design

We will share out plasmid designs, right from the start of the project. Initially, this will be through our collaboration network, and subsequently this will be on the CoroNAb website.

Predicted antigen-specific antibody variants.

Predicted antigenspecific antibody variants 1 month after receiving NGS data fromimmunized animal

Shared 2019-nCoV spike binding results for mAbs

Shared 2019-nCoV spike binding results for mAbs.

Shared nanobody sequences of confirmed binders, and data from NGS library sequencing

Shared nanobody sequences of confirmed binders, and data from NGS library sequencing.

Shared 2019-nCoV spike binding results for nanobodies

Shared 2019-nCoV spike binding results for nanobodies.

Shared mAb sequences, including NGS data

D3.1​ Shared mAb sequences, including NGS data.

Open Research Data Pilot (5)

Safety and immunogenicity data for each subunit /adjuvant combination. Selection of the best nCoV spike protein and adjuvant combination for immunizations of larger animals

Safety and immunogenicity data for each subunit/adjuvant combination. Selection of the best nCoV spike protein and adjuvant combination for immunizations of larger animals.

Scenarios will be developed for rollout of new antiviral therapy and a range of impacts will be examined in terms of impact on mortality and hospital bed usage

Models of interventions and new forecasts will be published online.

Update of DMP

The draft management plan will be updated.

Neutralization results for isolated monoclonal antibodies and camelid nanobodies, as well as modified mAbs

D4.2.​ Neutralization results for isolated monoclonal antibodies and camelid nanobodies (aims 2

Deliver an ongoing series of progressively optimized anti-nCoV mAbs to KI for neutralization screening.

Deliver an ongoing series of progressively optimized antinCoV mAbs to KI for neutralization screening

Other (1)

Mathematical model will be released as open source R package. Model projections will be published online.

Mathematical model will be released as open source R package. Model projections will be published online.

Demonstrators, pilots, prototypes (2)

2019-nCoV neutralization assay SOP, and dissemination of relevant plasmids.

Deliver lead candidate anti-nCoV mAbs (from hybridoma combinatorial library screens) to KI for neutralization screening

Deliver lead candidate antinCoV mAbs from hybridoma combinatorial library screens to KI for neutralization screening

Documents, reports (1)

Shared expression results

Shared expression results, yields, and working protocols for all constructs. This will be ongoing throughout the project.

Publications

Peer reviewed articles (22)

Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies

Author(s): Pradeepa Pushparaj, Andrea Nicoletto, Daniel J. Sheward, Hrishikesh Das, Xaquin Castro Dopico, Laura Perez Vidakovics, Leo Hanke, Mark Chernyshev, Sanjana Narang, Sungyong Kim, Julian Fischbach, Simon Ekström, Gerald McInerney, B. Martin Hällberg, Ben Murrell. Martin Corcoran, Gunilla B. Karlsson Hedestam
Published in: Immunity, 2022, ISSN 1097-4180
Publisher: Cell Press
DOI: 10.1016/j.immuni.2022.12.005

Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

Author(s): Erik Volz, Swapnil Mishra, Meera Chand, Jeffrey C. Barrett, Robert Johnson, Lily Geidelberg, Wes R. Hinsley, Daniel J. Laydon, Gavin Dabrera, Áine O’Toole, Robert Amato, Manon Ragonnet-Cronin, Ian Harrison, Ben Jackson, Cristina V. Ariani, Olivia Boyd, Nicholas J. Loman, John T. McCrone, Sónia Gonçalves, David Jorgensen, Richard Myers, Verity Hill, David K. Jackson, Katy Gaythorpe, Natalie Gr
Published in: Nature, 593/7858, 2021, Page(s) 266-269, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-021-03470-x

DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice

Author(s): Inga Szurgot, Leo Hanke, Daniel J. Sheward, Laura Perez Vidakovics, Ben Murrell, Gerald M. McInerney, Peter Liljeström
Published in: Scientific Reports, 11/1, 2021, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-021-82498-5

SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses

Author(s): Marco Mandolesi, Daniel J. Sheward, Leo Hanke, Junjie Ma, Pradeepa Pushparaj, Laura Perez Vidakovics, Changil Kim, Monika Àdori, Klara Lenart, Karin Loré, Xaquin Castro Dopico, Jonathan M. Coquet, Gerald M. McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell
Published in: Cell Reports Medicine, 2/4, 2021, Page(s) 100252, ISSN 2666-3791
Publisher: Cell Press
DOI: 10.1016/j.xcrm.2021.100252

Neutralisation sensitivity of the SARS-CoV-2 omicron (B.1.1.529) variant: a cross-sectional study

Author(s): Sheward Dj, Kim C, Ehling Ra, Pankow A, Castro Dopico X, Dyrdak R, Martin Dp, Reddy St, Dillner J, Karlsson Hedestam Gb, Albert J, Murrell B
Published in: The Lancet. Infectious diseases, 2022, ISSN 1473-3099
Publisher: The Lancet Publishing Group
DOI: 10.1016/s1473-3099(22)00129-3

A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo

Author(s): Leo Hanke, Hrishikesh Das, Daniel J. Sheward, Laura Perez Vidakovics, Egon Urgard, Ainhoa Moliner-Morro, Changil Kim, Vivien Karl, Alec Pankow, Natalie L. Smith, Bartlomiej Porebski, Oscar Fernandez-Capetillo, Erdinc Sezgin, Gabriel K. Pedersen, Jonathan M. Coquet, B. Martin Hällberg, Ben Murrell & Gerald M. McInerney
Published in: Nature Communications, 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-27610-z

SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display

Author(s): Ehling, R.A., Weber, C.R., Mason, D.M., Friedensohn, S., Wagner, B., Bieberich, F., Kapetanovic, E., Vazquez-Lombardi, R., Di Roberto, R.B., Hong, K.-L., Wagner, C., Pataia, M., Overath, M.D., Sheward, D.J., Murrell, B., Yermanos, A., Cuny, A.P., Savic, M., Rudolf, F., Reddy, S.T.
Published in: Cell Reports, 2022, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2021.110242

Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions

Author(s): Manon Ragonnet-Cronin, Olivia Boyd, Lily Geidelberg, David Jorgensen, Fabricia F. Nascimento, Igor Siveroni, Robert A. Johnson, Marc Baguelin, Zulma M. Cucunubá, Elita Jauneikaite, Swapnil Mishra, Oliver J. Watson, Neil Ferguson, Anne Cori, Christl A. Donnelly, Erik Volz
Published in: Nature Communications, 12/1, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-22366-y

Picomolar SARS-CoV-2 Neutralization Using Multi-Arm PEG Nanobody Constructs

Author(s): Ainhoa Moliner-Morro, Daniel J. Sheward, Vivien Karl, Laura Perez Vidakovics, Ben Murrell, Gerald M. McInerney, Leo Hanke
Published in: Biomolecules, 10/12, 2020, Page(s) 1661, ISSN 2218-273X
Publisher: MDPI
DOI: 10.3390/biom10121661

Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2

Author(s): Tânia F. Custódio, Hrishikesh Das, Daniel J. Sheward, Leo Hanke, Samuel Pazicky, Joanna Pieprzyk, Michèle Sorgenfrei, Martin A. Schroer, Andrey Yu. Gruzinov, Cy M. Jeffries, Melissa A. Graewert, Dmitri I. Svergun, Nikolay Dobrev, Kim Remans, Markus A. Seeger, Gerald M. McInerney, Ben Murrell, B. Martin Hällberg, Christian Löw
Published in: Nature Communications, 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-19204-y

Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape

Author(s): Paul-Albert Koenig, Hrishikesh Das, Hejun Liu, Beate M. Kümmerer, Florian N. Gohr, Lea-Marie Jenster, Lisa D. J. Schiffelers, Yonas M. Tesfamariam, Miki Uchima, Jennifer D. Wuerth, Karl Gatterdam, Natalia Ruetalo, Maria H. Christensen, Caroline I. Fandrey, Sabine Normann, Jan M. P. Tödtmann, Steffen Pritzl, Leo Hanke, Jannik Boos, Meng Yuan, Xueyong Zhu, Jonathan L. Schmid-Burgk, Hiroki Kato, Mi
Published in: Science, 371/6530, 2021, Page(s) eabe6230, ISSN 0036-8075
Publisher: American Association for the Advancement of Science
DOI: 10.1126/science.abe6230

Seropositivity in blood donors and pregnant women during the first year of SARS‐CoV‐2 transmission in Stockholm, Sweden

Author(s): X. Castro Dopico, S. Muschiol, M. Christian, L. Hanke, D. J. Sheward, N. F. Grinberg, J. Rorbach, G. Bogdanovic, G. M. Mcinerney, T. Allander, C. Wallace, B. Murrell, J. Albert, G. B. Karlsson Hedestam
Published in: Journal of Internal Medicine, 2021, ISSN 0954-6820
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/joim.13304

An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction

Author(s): 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, Gerald M. McInerney
Published in: Nature Communications, 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-18174-5

Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice

Author(s): Katharina Wørzner, Daniel J. Sheward, Signe Tandrup Schmidt, Leo Hanke, Julie Zimmermann, Gerald McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell, Dennis Christensen, Gabriel Kristian Pedersen
Published in: EBioMedicine, 63, 2021, Page(s) 103197, ISSN 2352-3964
Publisher: Elsevier BV
DOI: 10.1016/j.ebiom.2020.103197

Longitudinal single-cell analysis of SARS-CoV-2–reactive B cells uncovers persistence of early-formed, antigen-specific clones

Author(s): Lydia Scharf, Hannes Axelsson, Aikaterini Emmanouilidi, Nimitha R. Mathew, Daniel J. Sheward, Susannah Leach, Pauline Isakson, Ilya V. Smirnov, Emelie Marklund, Nicolae Miron, Lars-Magnus Andersson, Magnus Gisslén, Ben Murrell, Anna Lundgren, Mats Bemark, and Davide Angeletti
Published in: JCI Insight, 2022, ISSN 2379-3708
Publisher: American Society for Clinical Investigation (ASCI)
DOI: 10.1172/jci.insight.165299

SARS-CoV-2 exposure, symptoms and seroprevalence in healthcare workers in Sweden

Author(s): Ann-Sofie Rudberg, Sebastian Havervall, Anna Månberg, August Jernbom Falk, Katherina Aguilera, Henry Ng, Lena Gabrielsson, Ann-Christin Salomonsson, Leo Hanke, Ben Murrell, Gerald McInerney, Jennie Olofsson, Eni Andersson, Cecilia Hellström, Shaghayegh Bayati, Sofia Bergström, Elisa Pin, Ronald Sjöberg, Hanna Tegel, My Hedhammar, Mia Phillipson, Peter Nilsson, Sophia Hober, Charlotte Thålin
Published in: Nature Communications, 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-18848-0

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Author(s): Erik Volz, Verity Hill, John T. McCrone, Anna Price, David Jorgensen, Áine O’Toole, Joel Southgate, Robert Johnson, Ben Jackson, Fabricia F. Nascimento, Sara M. Rey, Samuel M. Nicholls, Rachel M. Colquhoun, Ana da Silva Filipe, James Shepherd, David J. Pascall, Rajiv Shah, Natasha Jesudason, Kathy Li, Ruth Jarrett, Nicole Pacchiarini, Matthew Bull, Lily Geidelberg, Igor Siveroni, Ian Goodfellow
Published in: Cell, 184/1, 2021, Page(s) 64-75.e11, ISSN 0092-8674
Publisher: Cell Press
DOI: 10.1016/j.cell.2020.11.020

Multianalyte serology in home-sampled blood enables an unbiased assessment of the immune response against SARS-CoV-2.

Author(s): Niclas Roxhed; Annika Bendes; Matilda Dale; Cecilia Mattsson; Leo Hanke; Tea Dodig-Crnković; Murray Christian; Birthe Meineke; Birthe Meineke; Simon J. Elsässer; Simon J. Elsässer; Juni Andréll; Sebastian Havervall; Charlotte Thålin; Carina Eklund; Joakim Dillner; Olof Beck; Cecilia Engel Thomas; Gerald M. McInerney; Mun-Gwan Hong; Ben Murrell; Claudia Fredolini; Jochen M. Schwenk
Published in: Nature Communications, 1, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-23893-4

Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralizing SARS-CoV-2 nanobodies

Author(s): Hanke, L., Sheward, D.J., Pankow, A., Vidakovics, L.P., Karl, V., Kim, C., Urgard, E., Smith, N.L., Astorga-Wells, J., Ekström, S., Coquet, J.M., McInerney, G.M., Murrell, B
Published in: Science Advances, 2022, ISSN 2375-2548
Publisher: American Association for the Advancement of Science
DOI: 10.1126/sciadv.abm0220

Probabilistic classification of anti‐SARS‐CoV‐2 antibody responses improves seroprevalence estimates

Author(s): Xaquin Castro Dopico; Sandra Muschiol; Nastasiya F Grinberg; Soo Aleman; Daniel J Sheward; Leo Hanke; Marcus Ahl; Linnea Vikström; Mattias Forsell; Jonathan M Coquet; Gerald McInerney; Joakim Dillner; Gordana Bogdanovic; Ben Murrell; Jan Albert; Chris Wallace; Gunilla B Karlsson Hedestam
Published in: Clinical & Translational Immunology, 1, 2022, ISSN 2050-0068
Publisher: Wiley
DOI: 10.1002/cti2.1379

Nanobodies in the limelight: Multifunctional tools in the fight against viruses

Author(s): Ainhoa Moliner-Morro, Gerald M McInerney, Leo Hanke
Published in: Journal of General Virology, 2022, ISSN 1743-422X
Publisher: BioMed Central
DOI: 10.1099/jgv.0.001731

Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models

Author(s): Sheward Dj, Mandolesi M, Urgard E, Kim C, Hanke L, Perez Vidakovics L, Pankow A, Smith Nl, Castro Dopico X, Mcinerney Gm, Coquet Jm, Karlsson Hedestam Gb, Murrell B
Published in: Cell Reports Medicine, 2021, ISSN 2666-3791
Publisher: Cell Press
DOI: 10.1016/j.xcrm.2021.100450