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Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial
File | Description | Size | Format | |
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19TLID0339_Ruhwald.pdf | Accepted version | 903.41 kB | Adobe PDF | View/Open |
CHLM01 clinical paper LancetID_final_clean_Submitted.docx | Accepted version | 1.11 MB | Microsoft Word | View/Open |
Supplementary information.pdf | Supporting information | 1.32 MB | Adobe PDF | View/Open |
Title: | Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial |
Authors: | Abraham, S Juel, HB Bang, P Cheeseman, HM Dohn, RB Cole, T Kristiansen, MP Korsholm, KS Lewis, D Olsen, AW McFarlane, LR Day, S Knudsen, S Moen, K Ruhwald, M Kromann, I Andersen, P Shattock, RJ Follmann, F |
Item Type: | Journal Article |
Abstract: | BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. INTERPRETATION: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. FUNDING: European Commission and The Innovation Fund Denmark. |
Issue Date: | 1-Oct-2019 |
Date of Acceptance: | 22-May-2019 |
URI: | http://hdl.handle.net/10044/1/76146 |
DOI: | 10.1016/S1473-3099(19)30279-8 |
ISSN: | 1473-3099 |
Publisher: | Elsevier |
Start Page: | 1091 |
End Page: | 1100 |
Journal / Book Title: | Lancet Infectious Diseases |
Volume: | 19 |
Issue: | 10 |
Copyright Statement: | © 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Sponsor/Funder: | Commission of the European Communities |
Funder's Grant Number: | 280873 |
Keywords: | Science & Technology Life Sciences & Biomedicine Infectious Diseases PROTECTIVE IMMUNITY GENITAL-TRACT TRACHOMATIS INFECTION Microbiology 1103 Clinical Sciences 1108 Medical Microbiology |
Publication Status: | Published |
Conference Place: | United States |
Online Publication Date: | 2019-08-12 |
Appears in Collections: | National Heart and Lung Institute |