Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccineexperienced humans and mice

被引：28

作者：

Muik, Alexander ^{[1
]}

Lui, Bonny Gaby ^{[1
]}

Bacher, Maren ^{[1
]}

Wallisch, Ann-Kathrin ^{[1
]}

Toker, Aras ^{[1
]}

Couto, Carla Iris Cadima ^{[1
]}

Gueler, Alptekin ^{[1
]}

Mampilli, Veena ^{[1
]}

Schmitt, Geneva J. ^{[1
]}

Mottl, Jonathan ^{[1
]}

Ziegenhals, Thomas ^{[1
]}

Fesser, Stephanie ^{[1
]}

Reinholz, Jonas ^{[1
]}

Wernig, Florian ^{[1
]}

Schraut, Karla-Gerlinde ^{[1
]}

Hefesha, Hossam ^{[1
]}

Cai, Hui ^{[2
]}

Yang, Qi ^{[2
]}

Walzer, Kerstin C. ^{[1
]}

Grosser, Jessica ^{[1
]}

Strauss, Stefan ^{[1
]}

Finlayson, Andrew ^{[1
]}

Kruger, Kimberly ^{[1
]}

Ozhelvaci, Orkun ^{[1
]}

Grikscheit, Katharina ^{[3
]}

Kohmer, Niko ^{[3
]}

Ciesek, Sandra ^{[3
,4
]}

Swanson, Kena A. ^{[2
]}

Vogel, Annette B. ^{[1
]}

Tuereci, Oezlem ^{[1
,5
]}

Sahin, Ugur ^{[1
,6
]}

机构：

[1] BioNTech, Goldgrube 12, D-55131 Mainz, Germany

[2] Pfizer, 401 N Middletown Rd, Pearl River, NY 10960 USA

[3] Goethe Univ Frankfurt, Univ Hosp, Inst Med Virol, D-60596 Frankfurt, Germany

[4] DZIF German Ctr Infect Res, External Partner Site, D-60596 Frankfurt, Germany

[5] HITRON Helmholtz Inst Translat Oncol Mainz DKFZ, Obere Zahlbacherstr 63, D-55131 Mainz, Germany

[6] Johannes Gutenberg Univ Mainz, TRON gGmbH Translat Oncol, Univ Med Ctr, Freiligrathstr 12, D-55131 Mainz, Germany

来源：

SCIENCE IMMUNOLOGY | 2022年 / 7卷 / 78期

关键词：

SARS-COV-2; OMICRON;

D O I：

10.1126/sciimmunol.ade9888

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior SARS-CoV-2 variant infection owing to over 30-amino acid alterations within the spike (S) glycoprotein. Breakthrough infection of vaccinated individuals with Omicron sublineages BA.1 and BA.2 is associated with distinct patterns of cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs). In continuation of our previous work, we characterized the effect of Omicron BA.4/BA.5 S glycoprotein exposure on the neutralizing antibody response upon breakthrough infection in vaccinated individuals and upon variant-adapted booster vaccination in mice. We found that immune sera from triple mRNA-vaccinated individuals with subsequent breakthrough infection during the Omicron BA.4/BA.5 wave showed cross-neutralizing activity against previous Omicron variants BA.1, BA.2, BA.2.12.1, and BA.4/BA.5 itself. Administration of a prototypic BA.4/BA.5-adapted mRNA booster vaccine to mice after SARS-CoV-2 wild-type strain-based primary immunization is associated with broader cross-neutralizing activity than a BA.1-adapted booster. Whereas the Omicron BA.1-adapted mRNAvaccine in a bivalent format (wild-type + BA.1) broadens cross-neutralizing activity relative to the BA.1 monovalent booster, cross-neutralization of BA.2 and descendants is more effective in mice boosted with a bivalent wild-type + BA.4/BA.5 vaccine. In naive mice, primary immunization with the bivalent wild-type + Omicron BA.4/BA.5 vaccine induces strong cross-neutralizing activity against Omicron VOCs and previous variants. These findings suggest that, when administered as boosters, mono- and bivalent Omicron BA.4/BA.5-adapted vaccines enhance neutralization breadth and that the bivalent version also has the potential to confer protection to individuals with no preexisting immunity against SARS-CoV-2.

引用

页数：10

共 29 条

[11] Jian F., LANCET INFECT DIS, P1535
[12] Kaku C. I., 2022, SCI IMMUNOL, V7, DOI DOI 10.1126/SCIIMMUNOL.ABQ3511
[13] MUIK A, 2022, SCI IMMUNOL EADE2283
[14] Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera
Muik, Alexander
Lui, Bonny Gaby
Wallisch, Ann-Kathrin
Bacher, Maren
Muehl, Julia
Reinholz, Jonas
Ozhelvaci, Orkun
Beckmann, Nina
Garcia, Ramon de la Caridad Gueimil
Poran, Asaf
Shpyro, Svetlana
Finlayson, Andrew
Cai, Hui
Yang, Qi
Swanson, Kena A.
Tuereci, Oezlem
Sahin, Ugur
[J]. SCIENCE, 2022, 375 (6581) : 678 - +
[15] Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera
Muik, Alexander
Wallisch, Ann-Kathrin
Saenger, Bianca
Swanson, Kena A.
Muehl, Julia
Chen, Wei
Cai, Hui
Maurus, Daniel
Sarkar, Ritu
Tuereci, Oezlem
Dormitzer, Philip R.
Sahin, Ugur
[J]. SCIENCE, 2021, 371 (6534) : 1152 - +
[16] Mykytyn AZ, 2022, SCI IMMUNOL, V7, DOI 10.1126/sciimmunol.abq4450
[17] Omicron BA.1 breakthrough infection drives cross-variant neutralization and memory B cell formation against conserved epitopes
Quandt, Jasmin
Muik, Alexander
Salisch, Nadine
Lui, Bonny Gaby
Lutz, Sebastian
Krueger, Kimberly
Wallisch, Ann-Kathrin
Adams-Quack, Petra
Bacher, Maren
Finlayson, Andrew
Ozhelvaci, Orkun
Vogler, Isabel
Grikscheit, Katharina
Hoehl, Sebastian
Goetsch, Udo
Ciesek, Sandra
Tuereci, Oezlem
Sahin, Ugur
[J]. SCIENCE IMMUNOLOGY, 2022, 7 (75)
[18] A Vesicular Stomatitis Virus Replicon-Based Bioassay for the Rapid and Sensitive Determination of Multi-Species Type I Interferon
Rentsch, Marianne Berger
Zimmer, Gert
[J]. PLOS ONE, 2011, 6 (10):
[19] Richardson SI., 2022, BIORXIV
[20] Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants
Servellita, Venice
Syed, Abdullah M.
Morris, Mary Kate
Brazer, Noah
Saldhi, Prachi
Garcia-Knight, Miguel
Sreekumar, Bharath
Khalid, Mir M.
Ciling, Alison
Chen, Pei-Yi
Kumar, G. Renuka
Gliwa, Amelia S.
Nguyen, Jenny
Sotomayor-Gonzalez, Alicia
Zhang, Yueyuan
Frias, Edwin
Prostko, John
Hackett, John, Jr.
Andino, Raul
Wadford, Debra A.
Hanson, Carl
Doudna, Jennifer
Ott, Melanie
Chiu, Charles Y.
[J]. CELL, 2022, 185 (09) : 1539 - +

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