{"doi":"10.1371/journal.ppat.1012566","title":"Humoral and T-cell-mediated responses to an insect-specific flavivirus-based Zika virus vaccine candidate","abstract":"Flaviviruses represent a significant global health threat and relatively few licensed vaccines exist to protect against them. Insect-specific flaviviruses (ISFVs) are incapable of replication in humans and have emerged as a novel and promising tool for flavivirus vaccine development. ISFV-based flavivirus vaccines have shown exceptional safety, immunogenicity, and efficacy, however, a detailed assessment of the correlates of protection and immune responses induced by these vaccines are still needed for vaccine optimization. Here, we explore the mechanisms of protective immunity induced by a previously created pre-clinical Zika virus (ZIKV) vaccine candidate, called Aripo/Zika (ARPV/ZIKV). In brief, immunocompromised IFN-αβR-/- mice passively immunized with ARPV/ZIKV immune sera experienced protection after lethal ZIKV challenge, although this protection was incomplete. ARPV/ZIKV-vaccinated IFN-αβR-/- mice depleted of CD4+ or CD8+ T-cells at the time of ZIKV challenge showed no morbidity or mortality. However, the adoptive transfer of ARPV/ZIKV-primed T-cells into recipient IFN-αβR-/- mice resulted in a two-day median increase in survival time compared to controls. Altogether, these results suggest that ARPV/ZIKV-induced protection is primarily mediated by neutralizing antibodies at the time of challenge and that T-cells may play a comparatively minor but cumulative role in the protection observed. Lastly, ARPV/ZIKV-vaccinated Tcra KO mice, which are deficient in T-cell responses, experienced significant mortality post-challenge. These results suggest that ARPV/ZIKV-induced cell-mediated responses are critical for development of protective immune responses at vaccination. Despite the strong focus on neutralizing antibody responses to novel flavivirus vaccine candidates, these results suggest that cell-mediated responses induced by ISFV-based vaccines remain important to overall protective responses.","journal":"PLoS Pathogens","year":2024,"id":445688,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":398464,"name":"Awadalkareem Adam","orcid":null,"position":1,"is_corresponding":false},{"id":245584,"name":"Lin Kang","orcid":"0000-0002-9186-9574","position":2,"is_corresponding":false},{"id":245585,"name":"Pawel Michalak","orcid":"0000-0003-4890-8985","position":3,"is_corresponding":false},{"id":951182,"name":"Juselyn D. Tupik","orcid":"0000-0003-4350-1553","position":4,"is_corresponding":false},{"id":1171664,"name":"Matthew A. Santos","orcid":null,"position":5,"is_corresponding":false},{"id":756779,"name":"Manette Tanelus","orcid":null,"position":6,"is_corresponding":false},{"id":736925,"name":"Krisangel López","orcid":null,"position":7,"is_corresponding":false},{"id":720128,"name":"Dawn I. Auguste","orcid":null,"position":8,"is_corresponding":false},{"id":1145318,"name":"Christy Lee","orcid":"0000-0002-0709-5001","position":9,"is_corresponding":false},{"id":297448,"name":"Irving C. Allen","orcid":"0000-0001-9573-5250","position":10,"is_corresponding":false},{"id":396912,"name":"Tian Wang","orcid":"0000-0002-1511-0793","position":11,"is_corresponding":false},{"id":440343,"name":"Albert J. Auguste","orcid":"0000-0001-9048-0041","position":12,"is_corresponding":false},{"id":704689,"name":"Danielle L. Porier","orcid":"0000-0001-8837-9673","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:01:46.243344Z","pmid":"39388457","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":[]}