A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:187 |
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| Enthalten in: |
Cell - 187(2024), 6 vom: 14. März, Seite 1363-1373.e12 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zuiani, Adam [VerfasserIn] |
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| Links: |
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| Themen: |
Immunology |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT05988203 Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2024.01.017 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 2 | |a A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease |
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| 500 | |a ClinicalTrials.gov: NCT05988203 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Nonhuman primate | |
| 650 | 4 | |a Orthopoxviruses | |
| 650 | 4 | |a Outbreak | |
| 650 | 4 | |a Pandemic preparedness | |
| 650 | 4 | |a Vaccinology | |
| 650 | 4 | |a Virology | |
| 650 | 4 | |a mRNA vaccine | |
| 650 | 4 | |a monkeypox virus | |
| 650 | 4 | |a mpox | |
| 650 | 7 | |a Smallpox Vaccine |2 NLM | |
| 650 | 7 | |a Vaccines, Combined |2 NLM | |
| 700 | 1 | |a Dulberger, Charles L |e verfasserin |4 aut | |
| 700 | 1 | |a De Silva, Nilushi S |e verfasserin |4 aut | |
| 700 | 1 | |a Marquette, Meghan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yu-Jung |e verfasserin |4 aut | |
| 700 | 1 | |a Palowitch, Gavin M |e verfasserin |4 aut | |
| 700 | 1 | |a Dokic, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez-Velazquez, Ricardo |e verfasserin |4 aut | |
| 700 | 1 | |a Schlatterer, Katja |e verfasserin |4 aut | |
| 700 | 1 | |a Sarkar, Sanjay |e verfasserin |4 aut | |
| 700 | 1 | |a Kar, Swagata |e verfasserin |4 aut | |
| 700 | 1 | |a Chawla, Bhavna |e verfasserin |4 aut | |
| 700 | 1 | |a Galeev, Alibek |e verfasserin |4 aut | |
| 700 | 1 | |a Lindemann, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Rothenberg, Daniel A |e verfasserin |4 aut | |
| 700 | 1 | |a Diao, Huitian |e verfasserin |4 aut | |
| 700 | 1 | |a Walls, Alexandra C |e verfasserin |4 aut | |
| 700 | 1 | |a Addona, Theresa A |e verfasserin |4 aut | |
| 700 | 1 | |a Mensa, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Vogel, Annette B |e verfasserin |4 aut | |
| 700 | 1 | |a Stuart, Lynda M |e verfasserin |4 aut | |
| 700 | 1 | |a van der Most, Robbert |e verfasserin |4 aut | |
| 700 | 1 | |a Srouji, John R |e verfasserin |4 aut | |
| 700 | 1 | |a Türeci, Özlem |e verfasserin |4 aut | |
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| 700 | 1 | |a Şahin, Uğur |e verfasserin |4 aut | |
| 700 | 1 | |a Poran, Asaf |e verfasserin |4 aut | |
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