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Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus

ABSTRACT: Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus

PROVIDER: PRJNA1051611 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27190700_1.fastq.gz	Fastqsanger.gz
	SRR27190700_2.fastq.gz	Fastqsanger.gz
	SRR27190701_1.fastq.gz	Fastqsanger.gz
	SRR27190701_2.fastq.gz	Fastqsanger.gz
	SRR27190702_1.fastq.gz	Fastqsanger.gz

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Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus

Project description:Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.

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Impaired innate and adaptive immune responses to BNT162b2 SARSCoV-2 vaccination in systemic lupus erythematosus [CTD]

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Heterologous ChAdOx1-BNT162b2 vaccination in Korean cohort induces robust immune and antibody responses that includes Omicron

Project description:Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than BNT162b2-BNT162b2. Here we investigated the molecular transcriptome, germline allelic variants of immunoglobulin loci, and anti-Omicron antibody levels in 46 office and lab workers from the Republic of Korea following ChAdOx1-BNT162b2 vaccination. Anti-spike-specific IgG antibody levels against the ancestral SARS-CoV-2 strain increased from 70 AU/ml to 14,000 AU/ml to 142,000 AU/ml one, three and seven days following the second vaccination. Titers against VOC, including Omicron, were two- to three-fold lower, yet higher than those measured following BNT162b2-BNT162b2 vaccination. RNA-seq of peripheral immune cells demonstrated activation of interferon pathways with increased IGHV clonal transcripts encoding neutralizing antibodies. scRNA-seq revealed enriched B cell and CD4+ T cell responses in both ChAdOx1-BNT162b2 and BNT162b2-BNT162b2 recipients, but a stronger clonal expansion of memory B cells with ChAdOx1-BNT162b2. In summary, heterologous ChAdOx1-BNT162b2 provides an innate and adaptive immune response that exceeds homologous BNT162b2 vaccination.

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Project description:Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than two doses of BNT162b2. Yet, the molecular transcriptome, the germline allelic variants of immunoglobulin loci and anti-Omicron antibody levels induced by the heterologous vaccination have not been formally investigated. Moreover, there is a paucity of COVID-19 vaccine studies including diverse genetic populations. Here, we show a robust molecular immune transcriptome and antibody repertoire in 46 office and lab workers from the Republic of Korea after heterologous vaccination, ChAdOx1 followed by BNT162b2. Anti-spike-specific IgG antibody levels against the ancestral SARS-CoV-2 strain increased from 70 AU/ml immediately following the first vaccination to 14,000 U/ml within three days after the second vaccination and 142,000 AU/ml after seven days. Antibody titers against more recent variants, including Omicron, were two- to three-fold lower, yet higher than those obtained after the second dose of a BNT162b2-BNT162b2 homologous vaccination. RNA-seq conducted on peripheral immune cells demonstrated a strong activation of interferon-induced genetic programs in the heterologous cohort and an increase of specific IGHV clonal transcripts encoding neutralizing antibodies was detected. Enrichment of B cell and CD4+ T cell responses was observed following both ChAdOx1-BNT162b2 heterologous and BNT162b2-BNT162b2 homologous vaccination using scRNA-seq, but clonally expanded memory B cells were relatively stronger in the heterologous cohort. In summary, a heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an innate and adaptive immune response exceeding that seen in homologous BNT162b2 vaccination.

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