{"doi":"10.1084/jem.20241529","title":"Heterologous mucosal vaccine boosting enhances mucosal and systemic immunity by distinct mechanisms","abstract":"Seasonal booster vaccination is the primary intervention for protection from respiratory viral infections, such as influenza virus or SARS-CoV-2. However, efficacy is often limited because immune exposure to prior strains impairs development of new responses. In this study, we sought to determine how this issue could be overcome in a mouse model of heterologous immunization against WT and omicron strains of SARS-CoV-2. Intranasal booster immunization circumvented the shortcomings of intramuscular immunization, resulting in superior systemic and mucosal T and B cell immunity and better viral control following SARS-CoV-2 challenge in hamsters. Mechanistically, an intranasal omicron booster immunization bypassed deleterious immune imprinting following intramuscular ancestral strain prime, which allowed for induction of de novo lung B cell and antibody responses against the omicron strain. Cross-reactive memory T cells were also efficiently recruited into the lungs. These findings support further testing of mucosal booster vaccines against respiratory viruses, particularly as a means of simultaneously overcoming deleterious immunological imprinting and enhancing mucosal responses.","journal":"The Journal of Experimental Medicine","year":2025,"id":524747,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1298935,"name":"Lyn Yong","orcid":"0009-0008-0551-746X","position":1,"is_corresponding":false},{"id":107161,"name":"Alexandra J. Spencer","orcid":"0000-0001-7958-6961","position":2,"is_corresponding":false},{"id":1398822,"name":"Freda Lam","orcid":"0009-0003-4354-9693","position":3,"is_corresponding":false},{"id":1398823,"name":"Ethan A. Courchesne","orcid":"0009-0009-2918-840X","position":4,"is_corresponding":false},{"id":1173381,"name":"Reshma Koolaparambil Mukesh","orcid":"0000-0002-2046-2793","position":5,"is_corresponding":false},{"id":107168,"name":"Marta Ulaszewska","orcid":"0000-0003-4288-2892","position":6,"is_corresponding":false},{"id":1398824,"name":"Alex Sampson","orcid":"0000-0001-5276-1643","position":7,"is_corresponding":false},{"id":1398825,"name":"Marie Lucienne","orcid":"0000-0002-1970-322X","position":8,"is_corresponding":false},{"id":107185,"name":"Reshma Kailath","orcid":"0009-0006-6180-1903","position":9,"is_corresponding":false},{"id":107187,"name":"Susan Morris","orcid":"0009-0000-1813-0557","position":10,"is_corresponding":false},{"id":107188,"name":"Claire Powers","orcid":"0009-0004-3522-9486","position":11,"is_corresponding":false},{"id":107162,"name":"Sandra Belij‐Rammerstorfer","orcid":"0000-0002-8637-3785","position":12,"is_corresponding":false},{"id":107194,"name":"Vincent J. Munster","orcid":"0000-0002-2288-3196","position":13,"is_corresponding":false},{"id":107159,"name":"Neeltje van Doremalen","orcid":"0000-0003-4368-6359","position":14,"is_corresponding":false},{"id":628809,"name":"Nicholas M. Provine","orcid":"0000-0002-9694-2216","position":15,"is_corresponding":false},{"id":107160,"name":"Teresa Lambe","orcid":"0000-0001-7711-897X","position":16,"is_corresponding":false},{"id":107179,"name":"Cameron Bissett","orcid":"0000-0003-3345-663X","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:16.562292Z","pmid":"41165617","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":[]}