{"doi":"10.1016/j.eclinm.2020.100313","title":"A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa","abstract":"BACKGROUND: ) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials. METHODS: CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207). FINDINGS: In total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group. INTERPRETATION: BCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials. FUNDING: NIAID and Aeras.","journal":"EClinicalMedicine","year":2020,"id":57906,"datarank":2.2872054086810163,"base_score":4.330733340286331,"endowment":4.330733340286331,"self_citation_contribution":0.6496100010429497,"citation_network_contribution":1.6375954076380668,"self_endowment_contribution":0.6496100010429497,"citer_contribution":1.6375954076380668,"corpus_percentile":null,"corpus_rank":null,"citation_count":75,"citer_count":66,"citers_with_citation_signal":62,"citers_with_endowment":62,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02378207"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302713,"name":"One Dintwe","orcid":"0000-0002-5642-7121","position":1,"is_corresponding":false},{"id":302714,"name":"Andrew Fioré-Gartland","orcid":"0000-0001-7627-2166","position":2,"is_corresponding":false},{"id":302715,"name":"Keren Middelkoop","orcid":"0000-0001-9922-4263","position":3,"is_corresponding":false},{"id":302716,"name":"Julia Hütter","orcid":"0000-0002-7989-0450","position":4,"is_corresponding":false},{"id":303582,"name":"Anthony Williams","orcid":null,"position":5,"is_corresponding":false},{"id":302717,"name":"April K. 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