iScience
Volume 25, Issue 11, 18 November 2022, 105369
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Article
Limited cross-variant immune response from SARS-CoV-2 Omicron BA.2 in naïve but not previously infected outpatients

https://doi.org/10.1016/j.isci.2022.105369Get rights and content
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Highlights

  • Reduced immune response in Omicron BA.2 patients without previous history of COVID-19

  • Elevated immune response in BA.1 and BA.2 patients with a previous history of COVID-19

  • Distinct antibody creation and immune gene expression between BA.1 and BA.2 patients

Summary

Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by the SARS-CoV-2 Omicron sublineage BA.2 compared to BA.1. Here we show that without previous history of COVID-19, BA.2 infection induces a reduced immune response against all variants of concern (VOC) compared to BA.1 infection. The absence of ACE2 binding in sera of previously naïve BA.1 and BA.2 patients indicates a lack of meaningful neutralization. In contrast, anti-spike antibody levels and neutralizing activity greatly increased in the BA.1 and BA.2 patients with a previous history of COVID-19. Transcriptome analyses of peripheral immune cells showed significant differences in immune response and specific antibody generation between BA.1 and BA.2 patients as well as significant differences in the expression of specific immune genes. In summary, prior infection status significantly impacts the innate and adaptive immune response against VOC following BA.2 infection.

Subject areas

Immune response
Virology
Transcriptomics

Data and code availability

  • RNA-seq data generated from this study were deposited under the accession GEO: GSE205244 in the Gene Expression Omnibus (GEO).

  • RNA-seq data of Omicron patients were obtained under GEO: GSE201530.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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