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This article is about Nature. We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply. There are two globally relevant variant of concern. Infections with Delta can lead to lung disease, but Omicron can cause milder symptoms, especially in vaccine recipients. The question is whether widespread Omicron infections could lead to future cross-variant protection. We show that a limited humoral immune response is caused by Omicron infections in mice and humans. The mice that were overexpressing the humanACE2receptor and wereinfecting them with Omicron mitigated only Omicron, but no other VOCs. Omicron replicates to low levels in the lungs and brains of animals that have been bitten, leading to mild disease with reduced pro- inflammatory cytokine expression and diminished activation of lung-resident T cells. The neutralization of only Omicron is shown by the sera from unvaccinated individuals. Omicron breakthrough infections induce higher neutralization titers against all VOCs. Our results show that Omicron can enhance immunity elicited by vaccines, but it may not give broad protection against non-Omicron variants in unvaccinated individuals. You agree to abide by the Community Guidelines when you submit a comment. If you find something that does not comply with our guidelines, please flag it as inappropriate.
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