Antibody and transcription landscape in peripheral blood mononuclear cells of elderly adults over 70 years of age with third dose of COVID-19 BBIBP-CorV and ZF2001 booster vaccine

Abstract

Background: In the context of the COVID-19 pandemic and extensive vaccination, it is important to explore the immune response of elderly adults to homologous and heterologous booster vaccines of COVID-19. At this point, we detected serum IgG antibodies and PBMC sample transcriptome profiles in 46 participants under 70 years old and 25 participants over 70 years old who received the third dose of the BBIBP-CorV and ZF2001 vaccines.

Results: On day 7, the antibody levels of people over 70 years old after the third dose of booster vaccine were lower than those of young people, and the transcriptional responses of innate and adaptive immunity were also weak. The age of the participants showed a significant negative correlation with functions related to T-cell differentiation and costimulation. Nevertheless, 28 days after the third dose, the IgG antibodies of elderly adults reached equivalence to those of younger adults, and immune-related transcriptional regulation was significantly improved. The age showed a significant positive correlation with functions related to "chemokine receptor binding", "chemokine activity", and "chemokine-mediated signaling pathway".

Conclusions: Our results document that the response of elderly adults to the third dose of the vaccine was delayed, but still able to achieve comparable immune effects compared to younger adults, in regard to antibody responses as well as at the transcript level.

Keywords: Aging; Antibody responses; COVID-19; RNA-seq; Systems biology analysis; Third booster vaccine; Transcriptome analysis.

Fig. 1

The details of this study design, including age characteristics of participants, booster vaccine type, and samples collection time in the 4 booster groups

Fig. 2

The level of IgG antibodies against SARS-CoV-2 of serum samples 7 (a) and 28 (b) days after booster vaccination. P values were computed by unpaired t-tests with log-transformation using GraphPad Prism 8.0

Fig. 3

Volcano plot of global gene expression changes in the elderly group induced by the third dose of BBIBP-CorV (a) and ZF2001 (b) at 7 days. Volcano plot of global gene expression changes in the elderly group induced by the third dose of BBIBP-CorV (c) and ZF2001 (d) at 28 days. Red: up-regulated DEGs in the elderly group compared with the younger group; Blue: down-regulated DEGs in the elderly group compared with the younger group; Grey: non-DEGs. Criteria: |Fold Change|= 2^^logFC_cutoff is marked out by two black dotted lines. P-value = 0.05 is marked out by a horizontal black line y =  − Log₁₀.^(0.05)

Fig. 4

a The expression profile of the top 20 up-regulated and down-regulated DEGs in the elderly group compared with the younger group boosted by BBIBP-CorV after 7 days. b The expression profile of the top 20 up-regulated and down-regulated DEGs in the elderly group compared with the younger group boosted by ZF2001 after 7 days. c The expression profile of the top 20 up-regulated and down-regulated DEGs in the elderly group compared with the younger group boosted by BBIBP-CorV after 28 days. d The expression profile of the top 20 up-regulated and down-regulated DEGs in the elderly group compared with the younger group boosted by ZF2001 after 28 days. Each row represents mRNA and each column represents a sample. Red indicates higher expression and blue indicates low expression

Fig. 5

a The GO analysis on DEGs induced by the third dose of BBIBP-CorV in elderly groups and the top 20 enriched terms in the biological process were shown. b The GO analysis on DEGs induced by the third dose of ZF2001 in elderly groups and the top 20 enriched terms in the biological process were shown. c The GO chordal diagram showed the degree of differential expression changes of genes involved in each functional project. Criteria: p-value < 0.05. d The GO chordal diagram showed the degree of differential expression changes of genes involved in each functional project. Criteria: p-value < 0.05

Fig. 6

The PPI network extracted from initial PPI networks for the protein products of up and down-regulated DEGs induced by the third dose of BBIBP-CorV in elderly groups after 28 days, consisting of 36 nodes (a) and 30 nodes (b). c The GO analysis on DEGs induced by the third dose of BBIBP-CorV in elderly groups and only the top 20 enriched terms in the biological process were shown. d The connection of GO functions with specific DEGs. e The GO chordal diagram showed the degree of differential expression changes of genes involved in each functional project. Criteria: p-value < 0.05

Fig. 7

The PPI network extracted from initial PPI networks for the protein products of up and down-regulated DEGs induced by the third dose of ZF2001 in elderly groups after 28 days, consisting of 37 nodes (a) and 32 nodes (b). c The GO analysis on DEGs induced by the third dose of ZF2001 in elderly groups and only the top 20 enriched terms in the biological process were shown. d The connection of GO functions with specific DEGs. e The GO chordal diagram showed the degree of differential expression changes of genes involved in each functional project. Criteria: p-value < 0.05

Fig. 8

WGCNA of the PBMCs transcriptome after 7 days of the third booster dose. a, b The 3D cluster map of genes, based on differences in topological overlap matrix (TOM), and assigned module colors. c Heatmap depicts the TOM of genes selected for weighted co-expression network analysis. Light color represents lower overlap and red represents higher overlap. d Module-trait associations: Each row corresponds to a module eigengene and each column to a trait. Each cell contains the corresponding correlation and p-value

Fig. 9

WGCNA of the transcriptome after 28 days of the third booster dose. a, b The 3D cluster map of genes, based on differences in topological overlap matrix (TOM), and assigned module colors. c Heatmap depicts the TOM of genes selected for weighted co-expression network analysis. Light color represents lower overlap and red represents higher overlap. d Module-trait associations: Each row corresponds to a module eigengene and each column to a trait. Each cell contains the corresponding correlation and p-value

Fig. 10

a The GO functional enrichment analysis of brown gene module after 7 days of the third booster dose. b The GO functional enrichment analysis of brown and yellow gene module after 28 days of the third booster dose