{"doi":"10.1371/journal.pone.0274906","title":"First-in-human study to evaluate safety, tolerability, and immunogenicity of heterologous regimens using the multivalent filovirus vaccines Ad26.Filo and MVA-BN-Filo administered in different sequences and schedules: A randomized, controlled study","abstract":"BACKGROUND: Though clinically similar, Ebola virus disease and Marburg virus disease are caused by different viruses. Of the 30 documented outbreaks of these diseases in sub-Saharan Africa, eight were major outbreaks (≥200 cases; five caused by Zaire ebolavirus [EBOV], two by Sudan ebolavirus [SUDV], and one by Marburg virus [MARV]). Our purpose is to develop a multivalent vaccine regimen protecting against each of these filoviruses. This first-in-human study assessed the safety and immunogenicity of several multivalent two-dose vaccine regimens that contain Ad26.Filo and MVA-BN-Filo. METHODS: Ad26.Filo combines three vaccines encoding the glycoprotein (GP) of EBOV, SUDV, and MARV. MVA-BN-Filo is a multivalent vector encoding EBOV, SUDV, and MARV GPs, and Taï Forest nucleoprotein. This Phase 1, randomized, double-blind, placebo-controlled study enrolled healthy adults (18-50 years) into four groups, randomized 5:1 (active:placebo), to assess different Ad26.Filo and MVA-BN-Filo vaccine directionality and administration intervals. The primary endpoint was safety; immune responses against EBOV, SUDV, and MARV GPs were also assessed. RESULTS: Seventy-two participants were randomized, and 60 (83.3%) completed the study. All regimens were well tolerated with no deaths or vaccine-related serious adverse events (AEs). The most frequently reported solicited local AE was injection site pain/tenderness. Solicited systemic AEs most frequently reported were headache, fatigue, chills, and myalgia; most solicited AEs were Grade 1-2. Solicited/unsolicited AE profiles were similar between regimens. Twenty-one days post-dose 2, 100% of participants on active regimen responded to vaccination and exhibited binding antibodies against EBOV, SUDV, and MARV GPs; neutralizing antibody responses were robust against EBOV (85.7-100%), but lower against SUDV (35.7-100%) and MARV (0-57.1%) GPs. An Ad26.Filo booster induced a rapid further increase in humoral responses. CONCLUSION: This study demonstrates that heterologous two-dose vaccine regimens with Ad26.Filo and MVA-BN-Filo are well tolerated and immunogenic in healthy adults. CLINICALTRIALS.GOV: NCT02860650.","journal":"PLoS ONE","year":2022,"id":247892,"datarank":1.3036497582519755,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.7791736240320034,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.7791736240320034,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":29,"citers_with_citation_signal":26,"citers_with_endowment":26,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02860650"]},"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":805337,"name":"Georgi Shukarev","orcid":"0000-0001-5154-7047","position":1,"is_corresponding":false},{"id":329303,"name":"Chelsea McLean","orcid":"0000-0002-3548-3482","position":2,"is_corresponding":false},{"id":468353,"name":"Neil Goldstein","orcid":null,"position":3,"is_corresponding":false},{"id":466909,"name":"Stephan Bart","orcid":"0000-0003-1652-3263","position":4,"is_corresponding":false},{"id":466910,"name":"Auguste Gaddah","orcid":"0009-0009-1545-6338","position":5,"is_corresponding":false},{"id":886604,"name":"Dickson Anumenden","orcid":null,"position":6,"is_corresponding":false},{"id":306136,"name":"Jeroen N. Stoop","orcid":null,"position":7,"is_corresponding":false},{"id":618177,"name":"Anne Marit de Groot","orcid":"0000-0002-4782-3392","position":8,"is_corresponding":false},{"id":288615,"name":"Maria Grazia Pau","orcid":"0000-0002-8995-9693","position":9,"is_corresponding":false},{"id":303943,"name":"Jenny Hendriks","orcid":"0009-0008-8191-6200","position":10,"is_corresponding":false},{"id":331738,"name":"Stephen C. De Rosa","orcid":"0000-0003-3871-4618","position":11,"is_corresponding":false},{"id":288617,"name":"Kristen W. Cohen","orcid":"0000-0002-8901-9941","position":12,"is_corresponding":false},{"id":52019,"name":"M. Juliana McElrath","orcid":"0000-0003-2276-7117","position":13,"is_corresponding":false},{"id":306147,"name":"Benoît Callendret","orcid":null,"position":14,"is_corresponding":false},{"id":303950,"name":"Kerstin Lühn","orcid":"0000-0001-8451-1294","position":15,"is_corresponding":false},{"id":303949,"name":"Macaya Douoguih","orcid":"0000-0002-2707-5729","position":16,"is_corresponding":false},{"id":303948,"name":"Cynthia Robinson","orcid":"0000-0002-0219-4123","position":17,"is_corresponding":false},{"id":306135,"name":"Viki Bockstal","orcid":null,"position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T00:23:57.824223Z","pmid":"36197845","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":[]}