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Background <p>Compared with homologous boosting, heterologous boosting with a different COVID-19 vaccine following priming generates stronger antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as variants, particularly for inactivated COVID-19 vaccine(CoronaVac). However, it is still unclear about the potential immune enhancement mechanism underlying heterologous boosting.</p> Methods <p>In this study, we isolated spike protein binding-specific monoclonal antibodies at day 180 post a homologous booster with CoronaVac or a heterologous booster with Ad5-nCoV based on two-dose of CoronaVac using the single B cell sorting platform. Subsequently, we verified their neutralization activity to SARS-CoV-2 variants, germline gene sequences and affinity kinetics targeting SARS-CoV-2 NTD/RBD/S1. Additionally, we conducted an in-depth analysis of the immunological response characteristics, by integrating single-cell RNA/V(D)J sequencing(scRNA/ V(D)J-seq).</p> Results <p>Our study demonstrated that heterologous boosting with Ad5-nCoV elicited more mature B cells with higher affinity and activated more abundant immune-related pathways compared to the homologous boosting with CoronaVac. In addition, Ad5-nCoV boosting expanded unique clonal types of B and T cells, whereas CoronaVac boosting led to a small-sized clonal expansion. Furthermore, the utilization of germlines associated with neutralizing antibody were preferentially enriched in recipients with Ad5-nCoV boosting.</p> Conclusions <p>Above all, our study gives insights for elaborating the systemic immune landscape of heterologous-boosting COVID-19 immunization by the novel single B cell sorting platform and scRNA/V(D)J-seq technology. Trial registration number: NCT04892459.</p>

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Systemic immune profiling of heterologous versus homologous boosting of COVID-19 vaccination

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月16日

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  • Xu Han,
  • Hudachuan Jiang,
  • Hui Zheng,
  • Pengfei Jin,
  • Lingjie Xu,
  • Fengze Wang,
  • Simin Li,
  • Chengwei Shao,
  • Siyue Jia,
  • Jialu Feng,
  • Ming Xu,
  • Jingxin Li

摘要

Background

Compared with homologous boosting, heterologous boosting with a different COVID-19 vaccine following priming generates stronger antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as variants, particularly for inactivated COVID-19 vaccine(CoronaVac). However, it is still unclear about the potential immune enhancement mechanism underlying heterologous boosting.

Methods

In this study, we isolated spike protein binding-specific monoclonal antibodies at day 180 post a homologous booster with CoronaVac or a heterologous booster with Ad5-nCoV based on two-dose of CoronaVac using the single B cell sorting platform. Subsequently, we verified their neutralization activity to SARS-CoV-2 variants, germline gene sequences and affinity kinetics targeting SARS-CoV-2 NTD/RBD/S1. Additionally, we conducted an in-depth analysis of the immunological response characteristics, by integrating single-cell RNA/V(D)J sequencing(scRNA/ V(D)J-seq).

Results

Our study demonstrated that heterologous boosting with Ad5-nCoV elicited more mature B cells with higher affinity and activated more abundant immune-related pathways compared to the homologous boosting with CoronaVac. In addition, Ad5-nCoV boosting expanded unique clonal types of B and T cells, whereas CoronaVac boosting led to a small-sized clonal expansion. Furthermore, the utilization of germlines associated with neutralizing antibody were preferentially enriched in recipients with Ad5-nCoV boosting.

Conclusions

Above all, our study gives insights for elaborating the systemic immune landscape of heterologous-boosting COVID-19 immunization by the novel single B cell sorting platform and scRNA/V(D)J-seq technology. Trial registration number: NCT04892459.