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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.

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