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.

Sneha Vishwanath, George William Carnell, Martina Billmeier, Luis Ohlendorf, Patrick Neckermann, Benedikt Asbach, Charlotte George, Maria Suau Sans, Andrew Chan, Joey Olivier, Angalee Nadesalingam, Sebastian Einhauser, Nigel Temperton, Diego Cantonit, Joe Grove, Ingo Jordan, Volker Sandig, Paul Tonks, Johannes Geiger, Christian Dohmen, Verena Mummert, Anne Rosalind Samuel, Christian Plank, Rebecca Kinsley, Ralf Wagner, Jonathan Luke Heeney