Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants.
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 mutati...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-09-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1010563 |
| _version_ | 1798031023924051968 |
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| author | Eric Wang Arup K Chakraborty |
| author_facet | Eric Wang Arup K Chakraborty |
| author_sort | Eric Wang |
| collection | DOAJ |
| description | 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 identified the S2' cleavage site and fusion peptide as potential pan-coronavirus vaccine targets. |
| first_indexed | 2024-04-11T19:50:34Z |
| format | Article |
| id | doaj.art-9dc9960b45b5423692cadd769ab44757 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-11T19:50:34Z |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-9dc9960b45b5423692cadd769ab447572022-12-22T04:06:20ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-09-01189e101056310.1371/journal.pcbi.1010563Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants.Eric WangArup K ChakrabortyThe 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 identified the S2' cleavage site and fusion peptide as potential pan-coronavirus vaccine targets.https://doi.org/10.1371/journal.pcbi.1010563 |
| spellingShingle | Eric Wang Arup K Chakraborty Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants. PLoS Computational Biology |
| title | Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants. |
| title_full | Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants. |
| title_fullStr | Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants. |
| title_full_unstemmed | Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants. |
| title_short | Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants. |
| title_sort | design of immunogens for eliciting antibody responses that may protect against sars cov 2 variants |
| url | https://doi.org/10.1371/journal.pcbi.1010563 |
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