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

Hye Kyung Lee; Jinyoung Go; Heungsup Sung; Seong Who Kim; Mary Walter; Ludwig Knabl; Priscilla A Furth; Lothar Hennighausen; Jin Won Huh

doi:10.1016/j.isci.2022.104473

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

iScience. 2022 Jun 17;25(6):104473. doi: 10.1016/j.isci.2022.104473. Epub 2022 May 26.

Authors

Hye Kyung Lee¹, Jinyoung Go², Heungsup Sung³, Seong Who Kim², Mary Walter⁴, Ludwig Knabl⁵, Priscilla A Furth⁶, Lothar Hennighausen¹, Jin Won Huh⁷

Affiliations

¹ National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
² Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
³ Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁴ Clinical Core, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
⁵ TyrolPath Obrist Brunhuber GmbH, Zams, Austria.
⁶ Departments of Oncology & Medicine, Georgetown University, Washington, DC, USA.
⁷ Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

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-fold 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.

Keywords: Health sciences; Immune response; Immunology.