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

Abstract

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

Receptor binding domain proteins of SARS‐CoV‐2 variants produced inNicotiana benthamianaelicit neutralizing antibodies against variants of concern

“…Wang et al revealed that application of RBD with multiple mutations as the cocktail vaccine increased variantspecific antibodies than the single antigen vaccine formulation or infection with wild-type SARS-CoV-2. 49 In conclusion, our study demonstrated that the SARS-CoV-2 variant vaccine might not induce broad protection against all the SARS-CoV-2 variants. The variant vaccine could be considered for booster dose to increase the breadth of the immune response.…”

“…Recently, the concept of cocktail vaccine has been proposed by combining the antigens for eliciting a broad immune response against SARS‐CoV‐2 variants. Wang et al revealed that application of RBD with multiple mutations as the cocktail vaccine increased variant‐specific antibodies than the single antigen vaccine formulation or infection with wild‐type SARS‐CoV‐2 49 …”

“…Wang et al revealed that application of RBD with multiple mutations as the cocktail vaccine increased variant‐specific antibodies than the single antigen vaccine formulation or infection with wild‐type SARS‐CoV‐2. 49 …”