{"doi":"10.1101/2022.06.10.495727","title":"Hybrid immunity shifts the Fc-effector quality of SARS-CoV-2 mRNA vaccine-induced immunity","abstract":"ABSTRACT Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data reveal enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine, but were similar to those achieved by naïve vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19, and remained higher following the second dose compared to naïve individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures – either hybrid immunity or two doses of vaccine alone - represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc effector functions against conserved regions of the virus.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298279,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9429,"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":113860,"name":"Daniel Stein","orcid":null,"position":1,"is_corresponding":false},{"id":108386,"name":"Sally Shin","orcid":"0000-0002-9306-2264","position":2,"is_corresponding":false},{"id":881786,"name":"Kathie G. Ferbas","orcid":"0009-0005-8861-2240","position":3,"is_corresponding":false},{"id":240566,"name":"Nicole H. Tobin","orcid":"0000-0001-6904-6128","position":4,"is_corresponding":false},{"id":618412,"name":"Colin Mann","orcid":"0000-0003-0949-2075","position":5,"is_corresponding":false},{"id":106724,"name":"Stephanie Fischinger","orcid":"0000-0003-2307-3379","position":6,"is_corresponding":false},{"id":104945,"name":"Erica Ollmann Saphire","orcid":"0000-0002-1206-7451","position":7,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":8,"is_corresponding":false},{"id":317562,"name":"Anne W. Rimoin","orcid":"0000-0002-0662-9067","position":9,"is_corresponding":false},{"id":240568,"name":"Grace M. Aldrovandi","orcid":"0000-0003-1604-9637","position":10,"is_corresponding":false},{"id":106757,"name":"Galit Alter","orcid":"0000-0002-7680-9215","position":11,"is_corresponding":false},{"id":628511,"name":"Kathryn Bowman","orcid":"0000-0003-4222-5286","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:31:36.269611Z","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":[]}