{"doi":"10.1101/2022.02.07.22270617","title":"Genetic immune response and antibody repertoire of heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort","abstract":"Abstract Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than two doses of BNT162b2 or ChAdOx1. 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 vaccine studies including diverse genetic populations. Here, we show a robust molecular immune transcriptome and antibody repertoire in 51 office workers from the Republic of Korea after a heterologous ChAdOx1-BNT162b2 vaccination or a homologous ChAdOx1-ChAdOx1 vaccination. Anti-spike-specific IgG antibody levels in the heterologous group increased from 14,000 U/ml to 142,000 AU/ml within eight days after the BNT162b2 vaccination. In contrast, antibody levels in the homologous group increased two-fold after the second ChAdOx1 dose. Antibody titers against the Omicron spike protein as compared to the ancestral strain were reduced to a lesser extent in the heterologous group. RNA-seq conducted on immune cells demonstrated a stronger activation of interferon-induced genetic programs in the heterologous cohort. An increase of specific IGHV clonal transcripts encoding neutralizing antibodies was preferentially detected in the heterologous cohort. Enrichment of B cell and CD4+ T cell responses were observed following both heterologous and homologous vaccination using scRNA-seq, but clonally expanded memory B cells were relatively stronger in the ChAdOx1-BNT162b2 cohort. In summary, a heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an innate and adaptive immune response exceeding that seen in homologous ChAdOx1 vaccinations but equivalent to that seen in homologous BNT162b2 vaccination.","journal":"medRxiv","year":2022,"id":299805,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":990107,"name":"Jinyoung Go","orcid":"0000-0002-3296-191X","position":1,"is_corresponding":false},{"id":990108,"name":"Heungsup Sung","orcid":"0000-0002-6062-4451","position":2,"is_corresponding":false},{"id":990109,"name":"Seong Who Kim","orcid":"0000-0002-3731-9109","position":3,"is_corresponding":false},{"id":234133,"name":"Mary Walter","orcid":null,"position":4,"is_corresponding":false},{"id":576165,"name":"Ludwig Knabl","orcid":"0000-0001-8280-8991","position":5,"is_corresponding":false},{"id":576168,"name":"Priscilla A. Furth","orcid":"0000-0003-3883-0715","position":6,"is_corresponding":false},{"id":14888,"name":"Lothar Hennighausen","orcid":"0000-0001-8319-9841","position":7,"is_corresponding":false},{"id":669075,"name":"Jin Won Huh","orcid":"0000-0002-3449-0461","position":8,"is_corresponding":false},{"id":279569,"name":"Hye‐Kyung Lee","orcid":"0000-0002-7785-5942","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}