Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination

Rahul K. Suryawanshi, Irene P. Chen, Tongcui Ma, Abdullah M. Syed, Noah Brazer, Prachi Saldhi, Camille R. Simoneau, Alison Ciling, Mir M. Khalid, Bharath Sreekumar, Pei-Yi Chen, G. Renuka Kumar, Mauricio Montano, Ronne Gascon, Chia-Lin Tsou, Miguel A. Garcia-Knight, Alicia Sotomayor-Gonzalez, Venice Servellita, Amelia Gliwa, Jenny Nguyen, Ines Silva, Bilal Milbes, Noah Kojima, Victoria Hess, Maria Shacreaw, Lauren Lopez, Matthew Brobeck, Fred Turner, Frank W. Soveg, Ashley F. George, Xiaohui Fang, Mazharul Maishan, Michael Matthay, Mary Kate Morris, Debra Wadford, Carl Hanson, Warner C. Greene, Raul Andino, Lee Spraggon, Nadia R. Roan (), Charles Y. Chiu (), Jennifer A. Doudna () and Melanie Ott ()
Additional contact information
Rahul K. Suryawanshi: Gladstone Institutes
Irene P. Chen: Gladstone Institutes
Tongcui Ma: Gladstone Institutes
Abdullah M. Syed: Gladstone Institutes
Noah Brazer: University of California, San Francisco
Prachi Saldhi: University of California, San Francisco
Camille R. Simoneau: Gladstone Institutes
Alison Ciling: Gladstone Institutes
Mir M. Khalid: Gladstone Institutes
Bharath Sreekumar: Gladstone Institutes
Pei-Yi Chen: Gladstone Institutes
G. Renuka Kumar: Gladstone Institutes
Mauricio Montano: Gladstone Institutes
Ronne Gascon: Gladstone Institutes
Chia-Lin Tsou: Gladstone Institutes
Miguel A. Garcia-Knight: University of California, San Francisco
Alicia Sotomayor-Gonzalez: University of California, San Francisco
Venice Servellita: University of California, San Francisco
Amelia Gliwa: University of California, San Francisco
Jenny Nguyen: University of California, San Francisco
Ines Silva: Curative Inc.
Bilal Milbes: Curative Inc.
Noah Kojima: University of California, Los Angeles
Victoria Hess: Curative Inc.
Maria Shacreaw: Curative Inc.
Lauren Lopez: Curative Inc.
Matthew Brobeck: Curative Inc.
Fred Turner: Curative Inc.
Frank W. Soveg: Gladstone Institutes
Ashley F. George: Gladstone Institutes
Xiaohui Fang: University of California, San Francisco
Mazharul Maishan: University of California, San Francisco
Michael Matthay: University of California, San Francisco
Mary Kate Morris: California Department of Public Health
Debra Wadford: California Department of Public Health
Carl Hanson: California Department of Public Health
Warner C. Greene: Gladstone Institutes
Raul Andino: University of California, San Francisco
Lee Spraggon: Curative Inc.
Nadia R. Roan: Gladstone Institutes
Charles Y. Chiu: University of California, San Francisco
Jennifer A. Doudna: Gladstone Institutes
Melanie Ott: Gladstone Institutes

Nature, 2022, vol. 607, issue 7918, 351-355

Abstract: Abstract SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

Date: 2022
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DOI: 10.1038/s41586-022-04865-0

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