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...

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Bibliographic Details
Published in:npj vaccines 2024-09, Vol.9 (1), p.164-9, Article 164
Main Authors: Vishwanath, Sneha, Carnell, George William, Billmeier, Martina, Ohlendorf, Luis, Neckermann, Patrick, Asbach, Benedikt, George, Charlotte, Sans, Maria Suau, Chan, Andrew, Olivier, Joey, Nadesalingam, Angalee, Einhauser, Sebastian, Temperton, Nigel, Cantoni, Diego, Grove, Joe, Jordan, Ingo, Sandig, Volker, Tonks, Paul, Geiger, Johannes, Dohmen, Christian, Mummert, Verena, Samuel, Anne Rosalind, Plank, Christian, Kinsley, Rebecca, Wagner, Ralf, Heeney, Jonathan Luke
Format: Article
Language:English
Subjects:
631/250/590/1991
631/250/590/2293
Antibodies
Antigens
Biomedical and Life Sciences
Biomedicine
COVID-19
COVID-19 vaccines
Design
Disease transmission
Immunity (Disease)
Immunization
Infectious Diseases
Medical Microbiology
Mutation
Proteins
Public Health
Severe acute respiratory syndrome coronavirus 2
Vaccine
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-024-00950-9