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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201535 | GEO | 2022/05/20

REPOSITORIES: GEO

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Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [scRNA-seq]

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.

2022-05-20 | GSE201534 | GEO

Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [RNA_seq]

2022-05-20 | GSE201533 | GEO

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

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

| PRJNA832131 | ENA

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S)

Project description:We longitudinally profiled plasma proteomes in 54 adults vaccinated with the BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) vaccines. Blood was collected pre-vaccination (V0) and 1-7 days after the 1st doses (BNT162b2 or mRNA-1273, V1) to assess innate and early adaptive responses. We identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

2023-03-01 | PXD036608 | Pride

Impact of two and three dose COVID-19 vaccination schedule on transcriptional, humoral and T cell immune response in previously heavily treated, single agent treated and naïve CLL patients

Project description:This study investigates the innate immune response to COVID-19 mRNA and vector-based vaccines in 15 patients with chronic lymphocytic leukemia (CLL). It assessed the innate and adaptive immune response of CLL patients after booster vaccination and generated a comprehensive transcriptome (mRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). Specifically, this investigation on a ‘3-dose’ cohort of heavily pretreated CLL patients, who had tested seronegative following a two-dose homologous vaccination (either BNT162b2 or ChAdOx1) and had received a third heterologous dose. A ‘2-dose’ cohort encompassed treatment-naïve or minimal pretreated CLL patients, who showed a serological immune response after the first vaccination and had received a second dose. Bulk mRNA-seq was conducted on PBMCs harvested prior to the vaccination and at days 2 and 7 post vaccination. The innate immune response observed in all patients was independent of the IgG antibody response. Expression of interferon-regulated genetic pathways was induced within two days after vaccination.

2022-10-21 | GSE201642 | GEO

Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [RNA_seq]

Project description:Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [RNA_seq]

| PRJNA832139 | ENA

Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [scRNA-seq]

Project description:Heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort induces a robust genetic immune and antibody response that includes Omicron [scRNA-seq]

| PRJNA832138 | ENA

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Project description:Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.

2023-01-16 | GSE222872 | GEO

Host Saliva RNA Responses to COVID-19 Infection

Project description:RNA-Seq was used to study changes in gene expression in saliva samples from 266 human subjects after SARS-COV-2 infection, vaccination, or combined infection and vaccination (breakthrough). Approximately equal numbers of males and females, matched for age, were profiled after subjects tested positive for COVID-19 by PCR and sequencing of the variant. In addition to samples from uninfected controls with and without vaccination, samples from infected subjects with and without vaccination that represent eight major SARS-COV-2 lineages are included: epsilon, iota, alpha, delta, omicron BA.1, omicron BA.2, omicron BA.4, and omicron BA.5. Stranded single-end sequencing was performed using standard Illumina protocols. Reads were quantified to hg38 human transcriptome using Salmon after adapter trimming. Quantified reads were filtered to remove features with fewer than one count in 80% of the samples, and normalized using TPM, followed by quantile and log2 transformation.

2023-09-19 | GSE212191 | GEO

Activation of Coagulation and Proinflammatory Pathways in Thrombosis with Thrombocytopenia Syndrome and Following COVID-19 Vaccination

Project description:Thrombosis with thrombocytopenia syndrome (TTS) is an extremely rare but potentially serious adverse event following immunization with the adenovirus vector-based COVID-19 vaccines Ad26.COV2.S (Janssen / Johnson & Johnson) or ChAdOx1 (AstraZeneca). However, no cases of TTS have been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States, suggesting that anti-vector immunity may reduce TTS risk. Here we show robust stimulation of platelet activation and coagulation pathways and innate immune pathways in patients with TTS but only transient activation of these pathways following vaccination. We evaluated proteomic profiles in 2 patients with TTS and transcriptomic and proteomic profiles in 20 people following an initial dose and a booster dose of Ad26.COV2.S and in 14 people who received the mRNA vaccines BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induced transient activation of platelet activation and coagulation pathways and innate proinflammatory pathways that resolved by day 7. TTS patients showed enhanced and sustained upregulation of these pathways, whereas a second immunization with Ad26.COV2.S or a reduced initial dose of Ad26.COV2.S resulted in lower activation of these pathways. These data provide insight into TTS pathogenesis and suggest a potential strategy for reducing TTS risk by lowering the dose of Ad26.COV2.S.

2023-10-13 | GSE220659 | GEO

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