Dr. Wenhong Zhang's group at the National Medical Center for Infectious Diseases published in Cell Discovery in October 2022, entitled "Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling". The results of this study, which used high-throughput single-cell V(D)J sequencing technology, showed that a "hybrid" booster vaccine is beneficial in enhancing the human body's resistance to the virus.

Research background

SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster, however, its cellular mechanisms remain elusive.

Here, the study investigated the durability of antibody responses and single-cell immune profiles (i.e., high-throughput single-cell V(D)J sequencing technology) following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months.

Key results

Enabled by high-throughput single-cell V(D)J sequencing technology, the group selected four heterologous samples (two with high neutralizing antibody response and two with low neutralizing antibody response) and eight heterologous samples (four with high neutralizing antibody response and four with low neutralizing antibody response), peripheral blood mononuclear cells (PBMCs) were collected prior to D0 and on D3, D14, D90, and D180 after the booster vaccination respectively for high-throughput single-cell V(D)J sequencing. 

Single-cell sequencing sampling design

The high-throughput single-cell V(D)J sequencing technology allows us to understand the percentages of different cells in each sample, as well as the gene expression levels of each type of cells.

Annotation of cell type subpopulations in PBMC samples at different sampling points

1. Enhancers achieve a faster and stronger plasma cell response by both stimulating memory cells and activating B cells ab initio, producing more antibodies and having a stronger heterologous than homologous effect.

Analysis of BCR source classification after booster injections

2. Enhanced antibody production is positively correlated with antigen presentation by conventional dendritic cells (cDCs) in the blood, which support B cell maturation through activation and development of follicular helper T cells (Tfh).

cDC- Tfh- B cell correlation

3. The normal activation of cDC/Tfh/B cells is accompanied by the upregulation of genes related to energy metabolic pathways, as well as glutamine hydrolysis-related genes.

All these findings are indicative for further development of next-generation SARS-CoV-2 vaccine with higher and longer-lasting efficacy.

References

1 Cellular basis of enhanced humoral immunity to SARS-CoV-2 upon homologous or heterologous booster vaccination analyzed by single-cell immune profiling，Cell Discovery，2022