tetano
Editor, Senior Moderator
J Transl Med
. 2026 Jul 16.
doi: 10.1186/s12967-026-08620-1. Online ahead of print.
Systemic immune profiling of heterologous versus homologous boosting of COVID-19 vaccination
Xu Han[SUP] #[/SUP][SUP] 1 2 [/SUP], Hudachuan Jiang[SUP] #[/SUP][SUP] 3 [/SUP], Hui Zheng[SUP] 3 [/SUP], Pengfei Jin[SUP] 1 4 [/SUP], Lingjie Xu[SUP] 5 [/SUP], Fengze Wang[SUP] 5 [/SUP], Simin Li[SUP] 3 [/SUP], Chengwei Shao[SUP] 3 [/SUP], Siyue Jia[SUP] 1 2 [/SUP], Jialu Feng[SUP] 6 [/SUP], Ming Xu[SUP] 7 8 9 10 [/SUP], Jingxin Li[SUP] 11 12 13 [/SUP]
Affiliations
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.
Keywords: Ad5-nCoV; COVID-19; Heterologous boosting; MAbs; ScRNA/V(D)J-seq; Systemic immunity.
. 2026 Jul 16.
doi: 10.1186/s12967-026-08620-1. Online ahead of print.
Systemic immune profiling of heterologous versus homologous boosting of COVID-19 vaccination
Xu Han[SUP] #[/SUP][SUP] 1 2 [/SUP], Hudachuan Jiang[SUP] #[/SUP][SUP] 3 [/SUP], Hui Zheng[SUP] 3 [/SUP], Pengfei Jin[SUP] 1 4 [/SUP], Lingjie Xu[SUP] 5 [/SUP], Fengze Wang[SUP] 5 [/SUP], Simin Li[SUP] 3 [/SUP], Chengwei Shao[SUP] 3 [/SUP], Siyue Jia[SUP] 1 2 [/SUP], Jialu Feng[SUP] 6 [/SUP], Ming Xu[SUP] 7 8 9 10 [/SUP], Jingxin Li[SUP] 11 12 13 [/SUP]
Affiliations
- PMID: 42464341
- DOI: 10.1186/s12967-026-08620-1
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.
Keywords: Ad5-nCoV; COVID-19; Heterologous boosting; MAbs; ScRNA/V(D)J-seq; Systemic immunity.