Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants

• DOI: 10.1371/journal.pcbi.1010563
• Publication Date: 2022-09-26T17:48:46Z
• Authors: Eric Wang; Arup K. Chakraborty
• Keywords: 2019-20 coronavirus outbreak; Sars virus; Betacoronavirus

The rise of SARS-CoV-2 variants and the history outbreaks caused by zoonotic coronaviruses point to need for next-generation vaccines that confer protection against variant strains. Here, we combined analyses diverse sequences structures coronavirus spikes with data from deep mutational scanning design antigens containing most significant mutations may emerge. We trained a neural network predict RBD expression ACE2 binding sequence, which allowed us determine these are stable bind ACE2. Thus, they represent viable variants. then used computational model affinity maturation (AM) study antibody response immunization different combinations designed antigens. results suggest cocktail is likely promote evolution higher titers antibodies target than or infection wildtype virus alone. Finally, our analysis 12 genera identified S2' cleavage site fusion peptide as potential pan-coronavirus vaccine targets.