Publication date: Jul 16, 2026
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. 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). 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. 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. NCT04892459.
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| Concepts | Keywords |
|---|---|
| Ad5-nCoV | |
| COVID-19 | |
| Heterologous boosting | |
| MAbs | |
| Systemic immunity |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| disease | MESH | severe acute respiratory syndrome |
| disease | MESH | Ad5 |
| disease | MESH | NTD |
| pathway | REACTOME | Reproduction |
| disease | MESH | included |
| disease | MESH | Emergency |
| drug | DRUGBANK | Coenzyme M |
| disease | MESH | strains |
| disease | MESH | CDR3 |
| drug | DRUGBANK | Tretamine |
| pathway | KEGG | Oxidative phosphorylation |
| pathway | REACTOME | Metabolism |
| pathway | KEGG | TNF signaling pathway |
| disease | MESH | infections |
| pathway | REACTOME | TNF signaling |
| disease | MESH | autoimmune diseases |
| drug | DRUGBANK | Immune Globulin Human |
| disease | MESH | APC |
| disease | MESH | vesicular stomatitis |
| drug | DRUGBANK | Aspartame |
| drug | DRUGBANK | Chromium |
| disease | MESH | STAR |
| drug | DRUGBANK | Amino acids |
| disease | MESH | Lam |
| drug | DRUGBANK | Guanosine |
| disease | MESH | Dis |
| disease | MESH | breakthrough infections |
| disease | MESH | Chai |
| drug | DRUGBANK | (S)-Des-Me-Ampa |