Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants

Vishwanath, Sneha and Carnell, George William and Billmeier, Martina and Ohlendorf, Luis and Neckermann, Patrick and Asbach, Benedikt and George, Charlotte and Sans, Maria Suau and Chan, Andrew and Olivier, Joey and Nadesalingam, Angalee and Einhauser, Sebastian and Temperton, Nigel and Cantoni, Diego and Grove, Joe and Jordan, Ingo and Sandig, Volker and Tonks, Paul and Geiger, Johannes and Dohmen, Christian and Mummert, Verena and Samuel, Anne Rosalind and Plank, Christian and Kinsley, Rebecca and Wagner, Ralf and Heeney, Jonathan Luke (2024) Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants. NPJ VACCINES, 9 (1): 164. ISSN , 2059-0105

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: LENTIVIRAL VECTOR; IMMUNE ESCAPE; PROTEIN; ACE2;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Jan 2026 15:09
Last Modified: 26 Jan 2026 15:09
URI: https://pred.uni-regensburg.de/id/eprint/64682

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