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Low neutralisation of the omicron BA.2 sublineage in boosted individuals who had breakthrough infections.

ABSTRACT:

SUBMITTER: Karaba AH

PROVIDER: S-EPMC9221289 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Low neutralisation of the omicron BA.2 sublineage in boosted individuals who had breakthrough infections.

Karaba Andrew H AH Johnston Trevor S TS Aytenfisu Tihitina Y TY Woldemeskel Bezawit A BA Garliss Caroline C CC Cox Andrea L AL Blankson Joel N JN

The Lancet. Microbe 20220622 9

PMID: 35752198

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Project description:Background Omicron subvariants have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. Although Omicron breakthrough infections (BTIs) exhibit lower hospitalization rates than previous variants, post-COVID conditions persist. However, the immune response dynamics, lymphocyte subsets, and immune repertoire features following BA.5 sublineage BTI remain poorly understood. Methods In a longitudinal cohort, we monitored the recovery dynamics in patients with BTI at various time points. We employed single-cell transcriptomics, T cell receptor (TCR)/BCR sequencing, and antibody mass spectrometry to sequentially assess the immune response following BA.5.2 or BF.7 BTI. Findings Serological analysis revealed active cellular and humoral immunity 2 weeks post-BTI, with significant increases in cytokines (CKs) like IFN-γ, TNFβ, IL-2, and neutralizing antibodies. CK levels reverted to pre-infection levels, while broadly neutralizing antibodies remained high 1 month post-infection. Single-cell sequencing demonstrated robust immune activation and antiviral responses in NK, T, and B lymphocytes within 1 month post-BTI. Interestingly, the immune system maintained its strength to combat viral infection at 2 weeks post-BTI, transitioning toward repair and tissue damage elimination at 1 month. TCR/BCR library analysis revealed a higher clonal type in the BTI_2w group, mainly in NKT, memory T or B, and plasma cells, crucial for immune memory and antigen clearance. The BTI_1m group exhibited more IgG and IgA BCR subtypes, with somatic hypermutation indicating mature antibodies. Biological function verification of IgG and IgA-type monoclonal antibodies corresponding to expanded BCRs revealed antigen-specific and broad-spectrum antibodies. Interpretation Our study elucidated the dynamic immune profiling of individuals 2 weeks and 1 month after Omicron BA.5 sublineage BTI. This provided essential insights into pathogenicity, sequential immune status, recovery mechanisms of Omicron subvariant BTI, and novel concepts for broad-spectrum antibody development.

Dataset Information

Low neutralisation of the omicron BA.2 sublineage in boosted individuals who had breakthrough infections.

Publications

Low neutralisation of the omicron BA.2 sublineage in boosted individuals who had breakthrough infections.

Similar Datasets

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