PMID- 31812463 OWN - NLM STAT- MEDLINE DCOM- 20210226 LR - 20211216 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 38 IP - 5 DP - 2020 Jan 29 TI - A double-blind, randomized controlled trial to evaluate the safety and immunogenicity of an intranasally administered trivalent inactivated influenza vaccine with the adjuvant LTh(alphaK): A phase II study. PG - 1048-1056 LID - S0264-410X(19)31589-0 [pii] LID - 10.1016/j.vaccine.2019.11.047 [doi] AB - BACKGROUND: Intranasal influenza vaccines may provide protective efficacy by inducing both systemic antibodies and local secretory IgA. Live attenuated intranasal vaccines are not feasible for high-risk groups. A previously constructed inactivated vaccine with adjuvant revealed an association with neurological events in some studies. In this phase II trial, we aimed to evaluate the safety and immunogenicity of an intranasal influenza vaccine with a novel adjuvant, heat-labile enterotoxin (LT)-derived from E. coli (LTh(alphaK)). METHODS: This study is a multicenter, randomized controlled, double-blind, phase II trial of an intranasal influenza vaccine containing 22.5 mug of the hemagglutinin (HA) antigen of three influenza strains in combination with 2 different LTh(alphaK) adjuvant doses (group 1: 30 mug; group 2: 45 mug) in subjects 20-70 years old. The control vaccine was 22.5 mug of influenza HA antigen alone (group 3). The vaccine was intranasally administered on days 1 and 8. Serum anti-HA antibody and nasal secretory IgA were measured, and adverse events (AEs) were recorded prevaccination and 29 (+/-2) days postvaccination. RESULTS: Of 354 participants randomized in the study, 340 received two vaccine doses. AEs were mostly mild, and there was no discontinuation related to the vaccine. Only a higher frequency of diarrhea after the first dose was noted among group 2 (11.5%) than among group 3 (2.8%), and there was no significant difference after the second dose. The three groups had comparable serum anti-HA antibody immunogenicity. However, the adjuvanted vaccines induced greater mucosal IgA antibody production than the control vaccine. In a subgroup analysis, group 1 participants achieved adequate immunogenicity among both 20- to 60- and 61- to 70-year-old participants. CONCLUSION: The intranasal influenza vaccine adjuvanted with LTh(alphaK) is generally safe and could provide systemic and local antibody responses. Adjuvanted vaccines were significantly more immunogenic than the nonadjuvanted control vaccine in mucosal immunity. ClinicalTrials.gov Identifier: NCT03784885. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Pan, Sung-Ching AU - Pan SC AD - Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Hsu, Wei-Ting AU - Hsu WT AD - Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. FAU - Lee, Wen-Sen AU - Lee WS AD - Department of Internal Medicine, Wan Fang Medical Center, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Wang, Ning-Chi AU - Wang NC AD - Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Chen, Tzeng-Ji AU - Chen TJ AD - Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Liu, Ming-Che AU - Liu MC AD - Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan. FAU - Pai, Hui-Chen AU - Pai HC AD - Advagene Biopharma Co., Ltd., Taipei, Taiwan; Development Center for Biotechnology, New Taipei City, Taiwan. FAU - Hsu, Yu-Shen AU - Hsu YS AD - Advagene Biopharma Co., Ltd., Taipei, Taiwan; Development Center for Biotechnology, New Taipei City, Taiwan. FAU - Chang, Mingi AU - Chang M AD - Advagene Biopharma Co., Ltd., Taipei, Taiwan; Development Center for Biotechnology, New Taipei City, Taiwan. FAU - Hsieh, Szu-Min AU - Hsieh SM AD - Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hsmaids@hotmail.com. LA - eng SI - ClinicalTrials.gov/NCT03784885 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191204 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Viral) RN - 0 (Bacterial Toxins) RN - 0 (Enterotoxins) RN - 0 (Escherichia coli Proteins) RN - 0 (Influenza Vaccines) RN - 0 (Vaccines, Inactivated) RN - D9K3SN2LNY (heat-labile enterotoxin, E coli) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Adult MH - Aged MH - Antibodies, Viral/blood MH - Bacterial Toxins/administration & dosage MH - Double-Blind Method MH - Enterotoxins/administration & dosage MH - Escherichia coli MH - Escherichia coli Proteins/administration & dosage MH - Female MH - Hemagglutination Inhibition Tests MH - Humans MH - *Immunogenicity, Vaccine MH - Influenza Vaccines/adverse effects/*immunology MH - *Influenza, Human/prevention & control MH - Male MH - Middle Aged MH - Vaccines, Inactivated/adverse effects/*immunology MH - Young Adult OTO - NOTNLM OT - Adjuvant OT - Administration OT - Influenza vaccine OT - Intranasal OT - LTh(alphaK) EDAT- 2019/12/10 06:00 MHDA- 2021/02/27 06:00 CRDT- 2019/12/09 06:00 PHST- 2019/07/05 00:00 [received] PHST- 2019/11/18 00:00 [accepted] PHST- 2019/12/10 06:00 [pubmed] PHST- 2021/02/27 06:00 [medline] PHST- 2019/12/09 06:00 [entrez] AID - S0264-410X(19)31589-0 [pii] AID - 10.1016/j.vaccine.2019.11.047 [doi] PST - ppublish SO - Vaccine. 2020 Jan 29;38(5):1048-1056. doi: 10.1016/j.vaccine.2019.11.047. Epub 2019 Dec 4.