دورية أكاديمية
أعرض في EDS

Safety and immunogenicity of a novel trivalent recombinant MVA-based equine encephalitis virus vaccine: A Phase 1 clinical trial.

التفاصيل البيبلوغرافية
العنوان: Safety and immunogenicity of a novel trivalent recombinant MVA-based equine encephalitis virus vaccine: A Phase 1 clinical trial.
المؤلفون: Fierro C; Johnson County Clin-Trials (JCCT), 16400 College Blvd., Lenexa, KS 66219, USA., Weidenthaler H; Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany., Vidojkovic S; Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany., Schmidt D; Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany., Gafoor Z; Bavarian Nordic Inc, 1005 Slater Road, Suite 101, Durham, NC 27703, USA., Stroukova D; Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany., Zwiers S; Bavarian Nordic Inc, 1005 Slater Road, Suite 101, Durham, NC 27703, USA., Müller J; Immunic AG, Lochhamer Schlag 21, 82166 Gräfelfing, Germany., Volkmann A; Bavarian Nordic GmbH, Fraunhoferstrasse 13, 82152 Martinsried, Germany. Electronic address: Ariane.Volkmann@bavarian-nordic.com.
المصدر: Vaccine [Vaccine] 2024 Apr 11; Vol. 42 (10), pp. 2695-2706. Date of Electronic Publication: 2024 Mar 16.
نوع المنشور: Clinical Trial, Phase I; Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam, The Netherlands : Elsevier Science
Original Publication: [Guildford, Surrey, UK] : Butterworths, [c1983-
مواضيع طبية MeSH: Alphavirus* , Encephalitis Virus, Venezuelan Equine* , Encephalomyelitis, Equine*/prevention & control, Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; Immunogenicity, Vaccine ; Vaccinia virus
مستخلص: Background: Three encephalitic alphaviruses-western, eastern, and Venezuelan equine encephalitis virus (WEEV, EEEV and VEEV)-can cause severe disease and have the potential to be used as biological weapons. There are no approved vaccines for human use. A novel multivalent MVA-BN-WEV vaccine encodes the envelope surface proteins of the 3 viruses and is thereby potentially able to protect against them all, as previously demonstrated in animal models. This first-in-human study assessed the safety, tolerability, and immunogenicity of MVA-BN-WEV vaccine in healthy adult participants.
Methods: Forty-five participants were enrolled into 3 dose groups (1 × 10E7 Inf.U, 1 × 10E8 Inf.U, and 2 × 10E8 Inf.U), received 2 doses 4 weeks apart, and were then monitored for 6 months.
Results: The safety profile of MVA-BN-WEV was acceptable at all administered doses, with incidence of local solicited AEs increased with increasing dose and no other clinically meaningful differences between dose groups. One SAE (Grade 2 pleural effusion) was reported in the lowest dose group and assessed as possibly related. No AEs resulted in death or led to withdrawal from the second vaccination or from the trial. The most common local solicited AE was injection site pain, and general solicited AEs were headache, fatigue, and myalgia. MVA-BN-WEV induced humoral immune responses; WEEV-, EEEV- and VEEV-specific neutralizing antibody responses peaked 2 weeks following the second vaccination, and the magnitude of these responses increased with dose escalation. The highest dose resulted in seroconversion of all (100 %) participants for WEEV and VEEV and 92.9 % for EEEV, 2 weeks following second vaccination, and durability was observed for 6 months. MVA-BN-WEV induced cellular immune responses to VEEV E1 and E2 (EEEV and WEEV not tested) and a dose effect for peptide pool E2.
Conclusion: The study demonstrated that MVA-BN-WEV is well tolerated, induces immune responses, and is suitable for further development.
Clinical Trial Registry Number: NCT04131595.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors Darja Schmidt, Sanja Vidojkovic, Heinz Weidenthaler, Daria Stroukova, and Ariane Volkmann are employees and stakeholders of Bavarian Nordic GmbH. Zarina Gafoor and Susan Zwiers are employees and stakeholders of Bavarian Nordic Inc. Carlos Fierro and Jutta Müller do not have any disclosures.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: Alphavirus; Eastern equine encephalitis virus (EEEV); Encephalitis; MVA; Vaccine; Venezuelan equine encephalitis virus (VEEV); Western equine encephalitis virus (WEEV)
سلسلة جزيئية: ClinicalTrials.gov NCT04131595
المشرفين على المادة: 0 (Antibodies, Neutralizing)
0 (Antibodies, Viral)
تواريخ الأحداث: Date Created: 20240317 Date Completed: 20240408 Latest Revision: 20240617
رمز التحديث: 20240617
DOI: 10.1016/j.vaccine.2024.03.011
PMID: 38494412
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2518
DOI:10.1016/j.vaccine.2024.03.011