TY - JOUR
T1 - Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants
AU - Vishwanath, Sneha
AU - Carnell, George William
AU - Billmeier, Martina
AU - Ohlendorf, Luis
AU - Neckermann, Patrick
AU - Asbach, Benedikt
AU - George, Charlotte
AU - Sans, Maria Suau
AU - Chan, Andrew
AU - Olivier, Joey
AU - Nadesalingam, Angalee
AU - Einhauser, Sebastian
AU - Temperton, Nigel
AU - Cantoni, Diego
AU - Grove, Joe
AU - Jordan, Ingo
AU - Sandig, Volker
AU - Tonks, Paul
AU - Geiger, Johannes
AU - Dohmen, Christian
AU - Mummert, Verena
AU - Samuel, Anne Rosalind
AU - Plank, Christian
AU - Kinsley, Rebecca
AU - Wagner, Ralf
AU - Heeney, Jonathan Luke
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85203338948&partnerID=8YFLogxK
U2 - 10.1038/s41541-024-00950-9
DO - 10.1038/s41541-024-00950-9
M3 - Article
AN - SCOPUS:85203338948
SN - 2059-0105
VL - 9
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 164
ER -