PMID- 37166567 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230621 IS - 2193-8229 (Print) IS - 2193-6382 (Electronic) IS - 2193-6382 (Linking) VI - 12 IP - 6 DP - 2023 Jun TI - Safety and Immunogenicity of the ID93 + GLA-SE Tuberculosis Vaccine in BCG-Vaccinated Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. PG - 1605-1624 LID - 10.1007/s40121-023-00806-0 [doi] AB - INTRODUCTION: This randomized, double-blind, placebo-controlled, phase 2a trial was conducted to evaluate the safety and immunogenicity of the ID93 + glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) vaccine in human immunodeficiency virus (HIV)-negative, previously Bacillus Calmette-Guerin (BCG)-vaccinated, and QuantiFERON-TB-negative healthy adults in South Korea. METHODS: Adults (n = 107) with no signs or symptoms of tuberculosis were randomly assigned to receive three intramuscular injections of 2 mug ID93 + 5 mug GLA-SE, 10 mug ID93 + 5 mug GLA-SE, or 0.9% normal saline placebo on days 0, 28, and 56. For safety assessment, data on solicited adverse events (AEs), unsolicited AEs, serious AEs (SAEs), and special interest AEs were collected. Antigen-specific antibody responses were measured using serum enzyme-linked immunosorbent assay. T-cell immune responses were measured using enzyme-linked immunospot and intracellular cytokine staining. RESULTS: No SAEs, deaths, or AEs leading to treatment discontinuation were found. The solicited local and systemic AEs observed were consistent with those previously reported. Compared with adults administered with the placebo, those administered with three intramuscular vaccine injections exhibited significantly higher antigen-specific antibody levels and Type 1 T-helper cellular immune responses. CONCLUSION: The ID93 + GLA-SE vaccine induced antigen-specific cellular and humoral immune responses, with an acceptable safety profile in previously healthy, BCG-vaccinated, Mycobacterium tuberculosis-uninfected adult healthcare workers. TRIAL REGISTRATION: This clinical trial was retrospectively registered on 16 January 2019 at Clinicaltrials.gov (NCT03806686). CI - (c) 2023. The Author(s). FAU - Choi, Yu Hwa AU - Choi YH AD - Quratis Inc., Seoul, Republic of Korea. FAU - Kang, Young Ae AU - Kang YA AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. AD - Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul, Republic of Korea. FAU - Park, Kwang Joo AU - Park KJ AD - Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon, Republic of Korea. FAU - Choi, Jae Chol AU - Choi JC AD - Pulmonology Department, Chung-Ang University Hospital, Seoul, Republic of Korea. FAU - Cho, Kwan Goo AU - Cho KG AD - Quratis Inc., Seoul, Republic of Korea. FAU - Ko, Da Yeon AU - Ko DY AD - Quratis Inc., Seoul, Republic of Korea. FAU - Ahn, Jun Ho AU - Ahn JH AD - Quratis Inc., Seoul, Republic of Korea. FAU - Lee, Boram AU - Lee B AD - Quratis Inc., Seoul, Republic of Korea. FAU - Ahn, Eunsol AU - Ahn E AD - Quratis Inc., Seoul, Republic of Korea. FAU - Woo, Yun Ju AU - Woo YJ AD - Quratis Inc., Seoul, Republic of Korea. FAU - Jung, Kwangsoo AU - Jung K AD - Quratis Inc., Seoul, Republic of Korea. FAU - Kim, Nan Yul AU - Kim NY AD - Quratis Inc., Seoul, Republic of Korea. FAU - Reese, Valerie A AU - Reese VA AD - Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. FAU - Larsen, Sasha E AU - Larsen SE AD - Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. FAU - Baldwin, Susan L AU - Baldwin SL AD - Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. FAU - Reed, Steven G AU - Reed SG AD - HDT Bio, Seattle, WA, USA. FAU - Coler, Rhea N AU - Coler RN AD - Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. Rhea.Coler@seattlechildrens.org. AD - Department of Global Health, University of Washington, Seattle, WA, USA. Rhea.Coler@seattlechildrens.org. AD - Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. Rhea.Coler@seattlechildrens.org. FAU - Lee, Hyejon AU - Lee H AUID- ORCID: 0000-0001-8207-537X AD - Quratis Inc., Seoul, Republic of Korea. hyejonlee@gmail.com. AD - Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul, Republic of Korea. hyejonlee@gmail.com. AD - Division of Vaccine Research, International Tuberculosis Research Center, Seoul, Republic of Korea. hyejonlee@gmail.com. FAU - Cho, Sang-Nae AU - Cho SN AD - Quratis Inc., Seoul, Republic of Korea. raycho@quratis.com. AD - Institute of Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul, Republic of Korea. raycho@quratis.com. LA - eng SI - ClinicalTrials.gov/NCT03806686 GR - HI14C1324/Quratis Inc. and supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea/ PT - Journal Article DEP - 20230511 PL - New Zealand TA - Infect Dis Ther JT - Infectious diseases and therapy JID - 101634499 PMC - PMC10173211 OTO - NOTNLM OT - GLA-SE OT - Immunogenicity OT - Safety OT - Subunit vaccine OT - Tuberculosis COIS- Yu Hwa Choi, Kwan Goo Cho, Da Yeon Ko, Jun Ho Ahn, Yun Ju Woo, Kwangsoo Jung, Eunsol Ahn, Boram Lee, Nan Yul Kim, Hyejon Lee, and Sang-Nae Cho are employees of Quratis at the time of the study or analysis. Yu Hwa Choi, Kwan Goo Cho, Sang-Nae Cho, Da Yeon Ko, and Jun Ho Ahn own shares or options to shares in Quratis. Valerie A. Reese, Sasha E. Larsen, Susan L. Baldwin, and Rhea N. Coler received grants from Quratis for the immunoassays of the study. All other authors report no competing interests. EDAT- 2023/05/11 13:18 MHDA- 2023/05/11 13:19 PMCR- 2023/05/11 CRDT- 2023/05/11 11:10 PHST- 2023/02/07 00:00 [received] PHST- 2023/04/11 00:00 [accepted] PHST- 2023/05/11 13:19 [medline] PHST- 2023/05/11 13:18 [pubmed] PHST- 2023/05/11 11:10 [entrez] PHST- 2023/05/11 00:00 [pmc-release] AID - 10.1007/s40121-023-00806-0 [pii] AID - 806 [pii] AID - 10.1007/s40121-023-00806-0 [doi] PST - ppublish SO - Infect Dis Ther. 2023 Jun;12(6):1605-1624. doi: 10.1007/s40121-023-00806-0. Epub 2023 May 11.