A Two-center, Randomized, Double-blind, Placebo-controlled, Phase Ib Study to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-MERS-S_DF-1 in Healthy Study Subjects

The study will be a two center, randomized, double blind, placebo controlled study of the MVA MERS S_DF-1 candidate delivered by i.m. injection. To evaluate the MERS-S-specific antibody responses and safety profile induced by the two dosage levels of MVA-MERS-S_DF-1 the data will be compared to a placebo control group.

Start Date16 Apr 2021

Sponsor / Collaborator

Universitätsklinikum Hamburg-Eppendorf

[+5]

NCT03615911 / CompletedPhase 1IIT

An Open, Single Center Phase I Trial to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-MERS-S

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a potentially fatal disease with a reported lethality of up to 40% that is under tight epidemiologic control by the World Health Organization (WHO) and currently without registered prevention or treatment option.
In this phase I first-in-human clinical trial, healthy volunteers in two different dose cohorts will be vaccinated twice with the candidate vaccine MVA-MERS-S. A subgroup will additionally receive a late booster vaccination.
The aim of the study is to assess the safety and tolerability of the candidate vaccine and to characterize its immunogenicity.

Start Date28 Nov 2017

Sponsor / Collaborator

Universitätsklinikum Hamburg-Eppendorf

[+5]

100 Clinical Results associated with MVA MERS S(Ludwig-Maximilians-Universität München)

100 Translational Medicine associated with MVA MERS S(Ludwig-Maximilians-Universität München)

100 Patents (Medical) associated with MVA MERS S(Ludwig-Maximilians-Universität München)

Literatures (Medical) associated with MVA MERS S(Ludwig-Maximilians-Universität München)

01 Oct 2024·The Lancet Infectious Diseases

Safety, immunogenicity, and optimal dosing of a modified vaccinia Ankara-based vaccine against MERS-CoV in healthy adults: a phase 1b, double-blind, randomised placebo-controlled clinical trial

Article

Author: Krähling, Verena ; Rottstegge, Monika ; Mayer, Leonie ; Mykytyn, Anna Z ; Ly, My Linh ; Addo, Marylyn M ; Dahlke, Christine ; Renevier, Niclas ; Kaltenberg, Laura ; Klüver, Michael ; Sandkuhl, Maren ; Tscherne, Alina ; Gerresheim, Gesche K ; Weskamm, Leonie M ; Neubert, Andreas ; Borregaard, Saskia ; van Gorp, Eric C M ; Kupke, Alexandra ; Zoran, Tamara ; Funk, Jana ; Haagmans, Bart L ; Kalomidou, Georgia ; Becker, Stephan ; Schlesner, Claudia ; Schwamborn, Klaus ; Sutter, Gerd ; Kardinahl, Simone ; Mellinghoff, Sybille ; Dieck, Marie-Louise ; Kelidou, Anastasia ; Fathi, Anahita ; Volz, Asisa ; Friedrich, Monika ; Grüttner, Cordula ; Hesterkamp, Thomas ; Hardtke, Svenja ; Raadsen, Matthijs P ; Schröder, Simon

BACKGROUNDMERS-CoV is a respiratory pathogen with a case-fatality rate of 36%, and for which no vaccines are currently licensed. MVA-MERS-S is a candidate vaccine based on recombinant modified vaccinia virus Ankara (MVA). In this study, the safety, immunogenicity, and optimal dose schedule of MVA-MERS-S was assessed in individuals with previous exposure to SARS-CoV-2 infections and vaccines.METHODSWe conducted a multicentre, double-blind, randomised controlled phase 1b clinical trial at two university medical centres in Germany and the Netherlands. Healthy volunteers aged 18-55 years were assigned by computer randomisation to receive three intramuscular injections of 10⁷ or 10⁸ plaque-forming units (PFU) of MVA-MERS-S, with two treatment groups each of either 28-day or 56-day intervals between the initial two doses, and one control arm that received only placebo, at a ratio of 2:2:2:2:1. The third dose was given after 224 days. The sponsor, clinical and laboratory staff, and participants were masked to both vaccine dose and dosing interval. The primary outcome was safety, assessed in the all participants who had received at least one injection; daily solicited vaccine reactions were recorded after each dose for 7 days, unsolicited adverse events for 28 days, and serious adverse events throughout the study. The secondary outcome was humoral immunogenicity, measured with vaccine-induced geometric mean antibody concentrations and seroconversion rates, analysed in all participants who received at least three allocated treatments. This study is registered at ClinicalTrials.gov (NCT04119440) and is completed.FINDINGSBetween 26 July, 2021, and 3 March, 2022, 244 volunteers were screened, 177 of whom were eligible and 140 were randomly assigned either to the 28-day 10⁷ PFU group (n=32), 56-day 10⁷ PFU group (n=31), 28-day 10⁸ PFU group (n=31), 56-day 10⁸ PFU group (n=30), or placebo group (n=16). In total, 178 doses were administered of 10⁷ PFU of MVA-MERS-S, 174 of 10⁸ PFU, and 164 doses of placebo, and 139 participants received at least one injection. 73 (53%) were female and 66 (48%) were male. No serious vaccine-related adverse events occurred. Solicited local reactions were mild in 288 (93%, 95% CI 90-96) of 309 reports and consisted primarily of pain or tenderness. Pain or tenderness (of any severity) occurred after 69 (39%, 32-46) of 178 10⁷ PFU injections, 138 (79%; 73-85) of 174 10⁸ PFU injections, and 18 (11%; 7-11) of 164 placebo injections. Of 595 reported solicited systemic reactions, 479 (81%, 77-83) were graded as mild. Systemic reactions of any grade occurred after 77 (43%; 36-51) 10⁷ PFU injections, 102 (59%; 51-66) 10⁸ PFU injections, and 67 (41%; 34-49) of 164 placebo injections. At 28 days after the second dose, MERS-CoV neutralising antibodies were highest for participants assigned to 56-day 10⁸ PFU, with geometric mean ratios of 7·2 (95% CI 3·9-13·3) for the 56-day 10⁸ PFU group versus the 28-day 10⁸ PFU group (p<0·0001), 3·9 (2·1-7·2) for the 56-day 10⁸ PFU group versus the 56-day 10⁷ PFU group (p=0·0031), and 5·4 (2·9-10·0) for the 56-day 10⁸ PFU group versus the 28-day 10⁷ PFU group (p=0·0003).INTERPRETATIONMVA-MERS-S was safe and immunogenic in individuals with previous and concurrent SARS-CoV-2 exposure. The second vaccination with the 10⁸ PFU dose of MVA-MERS-S elicited a stronger humoral immune response when administered 56 days after the first dose than a 28-day interval. Further studies are needed to verify these findings in groups at risk for MERS-CoV exposure, and at risk of severe disease, including older individuals and those with relevant comorbidities.FUNDINGCoalition for Epidemic Preparedness Innovations, the German Centre for Infection Research, and the German Research Foundation.

16 Aug 2024·The Journal of Infectious Diseases

Identification of a Spike-Specific CD8+ T-Cell Epitope Following Vaccination Against the Middle East Respiratory Syndrome Coronavirus in Humans

Article

Author: Ly, My L ; Sutter, Gerd ; Ditt, Vanessa A ; Krähling, Verena ; Dahlke, Christine ; Zinser, Madeleine E ; Volz, Asisa ; Becker, Stephan ; Grundlach, Swantje ; Weskamm, Leonie M ; Harrer, Caroline E ; Haagmanns, Bart ; Koch, Till ; Hesterkamp, Thomas ; Mayer, Leonie ; Addo, Marylyn M ; Friedrich, Monika ; Kessler, Melanie ; Schmiedel, Stefan ; Wolf, Timo ; Poetsch, Joseph H ; Fathi, Anahita ; Lassen, Susan ; Bartels, Etienne

AbstractLicensed vaccines against the Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging pathogen of concern, are lacking. The modified vaccinia virus Ankara vector-based vaccine MVA-MERS-S, expressing the MERS-CoV-spike glycoprotein (MERS-S), is one of 3 candidate vaccines in clinical development and elicits robust humoral and cellular immunity. Here, we identified for the first time a MERS-S–specific CD8+ T-cell epitope in an HLA-A*03:01/HLA-B*35:01-positive vaccinee using a screening assay, intracellular cytokine staining, and in silico epitope prediction. As evidence from MERS-CoV infection suggests a protective role of long-lasting CD8+ T-cell responses, the identification of epitopes will facilitate longitudinal analyses of vaccine-induced T-cell immunity.

01 Aug 2024·iScience

Dissecting humoral immune responses to an MVA-vectored MERS-CoV vaccine in humans using a systems serology approach

Article

Author: Dahlke, Christine ; Richert, Laura ; Grüttner, Cordula ; Rübenacker, Laura ; Koch, Till ; Sutter, Gerd ; Garcia, Mariana G. ; Harms, Charlotte ; Addo, Marylyn M. ; Blois, Sandra M. ; Friedrich, Monika ; Raadsen, Matthijs P. ; Weskamm, Leonie M. ; Huchon, Melanie ; Becker, Stephan ; Tarnow, Paulina ; Lhomme, Edouard ; Fathi, Anahita ; Haagmans, Bart L.

Besides neutralizing antibodies, which are considered an important measure for vaccine immunogenicity, Fc-mediated antibody functions can contribute to antibody-mediated protection. They are strongly influenced by structural antibody properties such as subclass and Fc glycan composition. We here applied a systems serology approach to dissect humoral immune responses induced by MVA-MERS-S, an MVA-vectored vaccine against the Middle East respiratory syndrome coronavirus (MERS-CoV). Building on preceding studies reporting the safety and immunogenicity of MVA-MERS-S, our study highlights the potential of a late boost, administered one year after prime, to enhance both neutralizing and Fc-mediated antibody functionality compared to the primary vaccination series. Distinct characteristics were observed for antibodies specific to the MERS-CoV spike protein S1 and S2 subunits, regarding subclass and glycan compositions as well as Fc functionality. These findings highlight the benefit of a late homologous booster vaccination with MVA-MERS-S and may be of interest for the design of future coronavirus vaccines.

100 Deals associated with MVA MERS S(Ludwig-Maximilians-Universität München)

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Indication	Highest Phase	Country/Location	Organization	Date
Coronavirus Infections	Preclinical	DE	Philipps University of Marburg	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03615911 (CTgov)	Phase 1	Coronavirus Infections	26	vaccine candidate MVA-MERS-S (Vaccination With 10^7 PFU MVA-MERS-S)	olojbtrwrs(qdkxcesepw) = kiyliuzlwt ebapfgwofl (glldshurmp, xvpnfgygxb - ggaqojxyfk) View more	-	06 Oct 2020
				vaccine candidate MVA-MERS-S (Vaccination With 10^8 PFU MVA-MERS-S)	olojbtrwrs(qdkxcesepw) = wmktxbkpvv ebapfgwofl (glldshurmp, qzsxlzdiam - kjcztatcwp) View more
NCT03615911 (Pubmed) Manual	Phase 1	Coronavirus Infections	26	MVA-MERS-S (low-dose)	(apyrkliuyh) = Participants had no serious adverse events. kpjltiqjkn (idljegyfmf ) View more	Positive	01 Jul 2020
				MVA-MERS-S (high-dose)

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