Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants
Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.
Authors
- George Carnell (ORCID: https://orcid.org/0000-0001-8875-0989)
- Patrick Neckermann (ORCID: https://orcid.org/0000-0001-6066-4034)
- Johannes Geiger
- Christian Plank (ORCID: https://orcid.org/0000-0002-6072-4903)
- Diego Cantoni (ORCID: https://orcid.org/0000-0001-8527-7719)
- Ralf Wagner (ORCID: https://orcid.org/0000-0002-2029-3846)
- Jonathan Luke Heeney (ORCID: https://orcid.org/0000-0003-2702-1621)
- Rebecca Kinsley
- Sneha Vishwanath (ORCID: https://orcid.org/0000-0001-9960-547X)
- Andrew Lung-Tat Chan (ORCID: https://orcid.org/0000-0003-3434-7283)
- Joe Grove (ORCID: https://orcid.org/0000-0001-5390-7579)
- Volker Sandig (ORCID: https://orcid.org/0000-0003-3889-2078)
- Luis Ohlendorf (ORCID: https://orcid.org/0000-0002-2057-3063)
- Benedikt Asbach (ORCID: https://orcid.org/0000-0003-1056-8591)
- Maria Suau Sans (ORCID: https://orcid.org/0000-0003-3607-0302)
- Sebastian Einhauser (ORCID: https://orcid.org/0000-0003-4177-4451)
- Ingo Jordan (ORCID: https://orcid.org/0000-0003-2711-7252)
- Christian Dohmen (ORCID: https://orcid.org/0000-0001-9711-7982)
- Angalee Nadesalingam (ORCID: https://orcid.org/0000-0002-2847-3614)
- Martina Billmeier
- Charlotte George (ORCID: https://orcid.org/0000-0002-6585-3288)
- Nigel James Temperton (ORCID: https://orcid.org/0000-0002-7978-3815)
- Paul Tonks
- Verena Mummert
- Joey Olivier (ORCID: https://orcid.org/0000-0002-5144-5267)
- Anne Rosalind Samuel
Institutions
- Medway School of Pharmacy (GB)
- University of Cambridge (GB)
- University Hospital Regensburg (DE)
- Bridge University (SS)
- Institute of Medical Microbiology and Hygiene (DE)
- MRC University of Glasgow Centre for Virus Research (GB)
- Ethris (Germany) (DE)
- University of Regensburg (DE)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-09-09
- DOI
- https://doi.org/10.1038/s41541-024-00950-9
- Citations
- 6
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.33
Funders
- UK Research and Innovation
- Horizon 2020 Framework Programme
- Medical Research Council