Abstract
In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.
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Data availability
The data supporting the findings of this study are available within the article and its Supplementary information files (Table Source data). The single-cell RNA-seq data and BCR-seq data can be accessed in Zenodo (https://doi.org/10.5281/zenodo.7904759).
Code availability
The codes used to generate the results in the manuscript are available at: https://github.com/wanhui5867/adenovirus_C19_vaccines.
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Acknowledgements
This research was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT), grant number 312677 (JH), the Swedish Research Council (2019-01302, 2020-06116, QPH), and the European Union’s Horizon 2020 research and innovation program (ATAC, grant number 101003650, QPH). The authors thank Roberto Carvente and Analitek for technical support during the single-cell experiments and the SENASICA and WHO Collaborating Centre on Antimicrobial Resistance in Foodborne and Environmental Bacteria (MEX-33), especially Mayrén Zamora Nava and Fabiola Hernández Pérez, for helping us to sequence our libraries.
Funding
This work was supported by CONACyT (grant number 312677, JH), the Swedish Research Council (grants 2019-01302 and 2020-06116, QPH), and the European Union’s Horizon 2020 research and innovation program through the ATAC project under grant number 101003650 (QPH).
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Conceptualization, JH; methodology, MGV, HW, MRS, DHT, OV, VMH, FDC, MSH; formal analysis, MGV, HW; investigation, MGV, HW; resources, MSH, QPH, JH; writing—original draft preparation, MGV and HW, and JH; writing—review and editing; HM, QPH, JH; funding acquisition, QPH, JH. All authors have read and agreed to the published version of the manuscript.
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García-Vega, M., Wan, H., Reséndiz-Sandoval, M. et al. Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines. Genes Immun 25, 158–167 (2024). https://doi.org/10.1038/s41435-024-00270-x
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DOI: https://doi.org/10.1038/s41435-024-00270-x