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

Vishwanath, Sneha, Carnell, George William, Billmeier, Martina, Ohlendorf, Luis, Neckermann, Patrick, Asbach, Benedikt, George, Charlotte, Sans, Maria Suau, Chan, Andrew, Olivier, Joey, and others. (2024) Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants. npj Vaccines, 9 (1). Article Number 164. ISSN 2059-0105. (doi:10.1038/s41541-024-00950-9) (KAR id:107203)

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
DOI/Identification number: 10.1038/s41541-024-00950-9
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: Wellcome Trust (https://ror.org/029chgv08)
Medical Research Council (https://ror.org/03x94j517)
Depositing User: Nigel Temperton
Date Deposited: 11 Sep 2024 18:26 UTC
Last Modified: 16 Sep 2024 11:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/107203 (The current URI for this page, for reference purposes)

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