Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine
Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccin...
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Nature Portfolio
2024-11-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-024-01013-9 |
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| author | Kayvon Modjarrad Ye Che Wei Chen Huixian Wu Carla I. Cadima Alexander Muik Mohan S. Maddur Kristin R. Tompkins Lyndsey T. Martinez Hui Cai Minah Ramos Sonia Mensah Brittney Cumbia Larissa Falcao Andrew P. McKeen Jeanne S. Chang Kimberly F. Fennell Kevin W. Huynh Thomas J. McLellan Parag V. Sahasrabudhe Wei Chen Michael Cerswell Miguel A. Garcia Shilong Li Rahul Sharma Weiqiang Li Kristianne P. Dizon Stacy Duarte Frank Gillett Rachel Smith Deanne M. Illenberger Kari Sweeney Efferen Annette B. Vogel Annaliesa S. Anderson Uğur Şahin Kena A. Swanson |
| author_facet | Kayvon Modjarrad Ye Che Wei Chen Huixian Wu Carla I. Cadima Alexander Muik Mohan S. Maddur Kristin R. Tompkins Lyndsey T. Martinez Hui Cai Minah Ramos Sonia Mensah Brittney Cumbia Larissa Falcao Andrew P. McKeen Jeanne S. Chang Kimberly F. Fennell Kevin W. Huynh Thomas J. McLellan Parag V. Sahasrabudhe Wei Chen Michael Cerswell Miguel A. Garcia Shilong Li Rahul Sharma Weiqiang Li Kristianne P. Dizon Stacy Duarte Frank Gillett Rachel Smith Deanne M. Illenberger Kari Sweeney Efferen Annette B. Vogel Annaliesa S. Anderson Uğur Şahin Kena A. Swanson |
| author_sort | Kayvon Modjarrad |
| collection | DOAJ |
| description | Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative to the original BNT162b2 backbone, in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation and adopts a flexible, predominantly open, state, with high affinity for the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose series in naive mice. Strong S-specific Th1 CD4+ and IFNγ+ CD8+ T cell responses were also observed. These findings, together with real world performance of the XBB.1.5-adapted vaccine, suggest that preclinical data for the monovalent Omicron XBB.1.5-adapted BNT162b2 was predictive of protective immunity against dominant SARS-CoV-2 strains. |
| format | Article |
| id | doaj-art-1f81685a3cb940afbcebd45045b3eb64 |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-1f81685a3cb940afbcebd45045b3eb642025-08-20T02:32:56ZengNature Portfolionpj Vaccines2059-01052024-11-019111310.1038/s41541-024-01013-9Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccineKayvon Modjarrad0Ye Che1Wei Chen2Huixian Wu3Carla I. Cadima4Alexander Muik5Mohan S. Maddur6Kristin R. Tompkins7Lyndsey T. Martinez8Hui Cai9Minah Ramos10Sonia Mensah11Brittney Cumbia12Larissa Falcao13Andrew P. McKeen14Jeanne S. Chang15Kimberly F. Fennell16Kevin W. Huynh17Thomas J. McLellan18Parag V. Sahasrabudhe19Wei Chen20Michael Cerswell21Miguel A. Garcia22Shilong Li23Rahul Sharma24Weiqiang Li25Kristianne P. Dizon26Stacy Duarte27Frank Gillett28Rachel Smith29Deanne M. Illenberger30Kari Sweeney Efferen31Annette B. Vogel32Annaliesa S. Anderson33Uğur Şahin34Kena A. Swanson35Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Discovery Sciences, Pfizer Inc.BioNTech SEBioNTech SEVaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Global Biometrics and Data Management, Pfizer Inc.Discovery Sciences, Pfizer Inc.Discovery Sciences, Pfizer Inc.Discovery Sciences, Pfizer Inc.Discovery Sciences, Pfizer Inc.Discovery Sciences, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.Vaccine Research and Development, Pfizer Inc.BioNTech SEVaccine Research and Development, Pfizer Inc.BioNTech SEVaccine Research and Development, Pfizer Inc.Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative to the original BNT162b2 backbone, in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation and adopts a flexible, predominantly open, state, with high affinity for the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose series in naive mice. Strong S-specific Th1 CD4+ and IFNγ+ CD8+ T cell responses were also observed. These findings, together with real world performance of the XBB.1.5-adapted vaccine, suggest that preclinical data for the monovalent Omicron XBB.1.5-adapted BNT162b2 was predictive of protective immunity against dominant SARS-CoV-2 strains.https://doi.org/10.1038/s41541-024-01013-9 |
| spellingShingle | Kayvon Modjarrad Ye Che Wei Chen Huixian Wu Carla I. Cadima Alexander Muik Mohan S. Maddur Kristin R. Tompkins Lyndsey T. Martinez Hui Cai Minah Ramos Sonia Mensah Brittney Cumbia Larissa Falcao Andrew P. McKeen Jeanne S. Chang Kimberly F. Fennell Kevin W. Huynh Thomas J. McLellan Parag V. Sahasrabudhe Wei Chen Michael Cerswell Miguel A. Garcia Shilong Li Rahul Sharma Weiqiang Li Kristianne P. Dizon Stacy Duarte Frank Gillett Rachel Smith Deanne M. Illenberger Kari Sweeney Efferen Annette B. Vogel Annaliesa S. Anderson Uğur Şahin Kena A. Swanson Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine npj Vaccines |
| title | Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine |
| title_full | Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine |
| title_fullStr | Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine |
| title_full_unstemmed | Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine |
| title_short | Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine |
| title_sort | preclinical characterization of the omicron xbb 1 5 adapted bnt162b2 covid 19 vaccine |
| url | https://doi.org/10.1038/s41541-024-01013-9 |
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