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Comparative single-cell transcriptomic profile of hybrid immunity induced by adenovirus vector-based COVID-19 vaccines

Genes & Immunity volume 25, pages 158–167 (2024)Cite this article

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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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Fig. 1: Single-cell transcriptomic profile of hybrid immunity induced by Ad5-nCoV and AZD1222 vaccines.
Fig. 2: Characterization of B cell response induced by vaccines (Ad5-nCoV and AZD1222) and hybrid immunity.
Fig. 3: BCR repertoire induced by vaccines (Ad5-nCoV and AZD1222) and hybrid immunity.
Fig. 4: Characterization of T cell response induced by vaccines (Ad5-nCoV and AZD1222) and hybrid immunity.

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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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Author notes

  1. These authors contributed equally: Melissa García-Vega, Hui Wan.

Authors and Affiliations

  1. Laboratorio de Inmunología, Centro de Investigación en Alimentación y Desarrollo, A.C, Hermosillo, Sonora, 83304, Mexico

    Melissa García-Vega, Mónica Reséndiz-Sandoval, Diana Hinojosa-Trujillo, Verónica Mata-Haro & Jesús Hernández

  2. Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, SE171 65, Sweden

    Hui Wan, Harold Marcotte & Qiang Pan-Hammarström

  3. Departamento de Ciencias Químico Biológicas, Universidad de Sonora, Hermosillo, Sonora, 83000, Mexico

    Olivia Valenzuela

  4. Comisión México-Estados Unidos para la Prevención de la Fiebre Aftosa y otras Enfermedades Exóticas de los Animales (CPA), SENASICA, SADER, Ciudad de México, 05010, Mexico

    Freddy Dehesa-Canseco & Mario Solís-Hernández

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Contributions

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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Correspondence to Qiang Pan-Hammarström or Jesús Hernández.

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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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