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
Affiliations
Hye Kyung Lee
National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Jinyoung Go
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Heungsup Sung
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Seong Who Kim
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Mary Walter
Clinical Core, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892, USA
Ludwig Knabl
TyrolPath Obrist Brunhuber GmbH, Zams, Austria
Priscilla A. Furth
Departments of Oncology & Medicine, Georgetown University, Washington, DC, USA; Corresponding author
Lothar Hennighausen
National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Jin Won Huh
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Corresponding author
Summary: 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.
