Safety, Reactogenicity and Immunogenicity of a Novel MVA-SARS-2-ST Vaccine Candidate Administered as Inhalation Boost in SARS-CoV-2 Immunized Adults - Phase I Study

This will be a phase I, single-center trial, including a total of 30 participants in two cohorts.
Cohort 1 (n=6): Healthy male or female adults aged 18 - ≤ 60 previously primary immunized with two vaccinations with any regimen using any EU marketed SARS-CoV-2 vaccine (mRNA-, vector-, protein-based, attenuated SARS-CoV-2 virus) or with a single application of COVID-19 Vaccine Janssen.
Cohort 2 (n=24): Healthy male or female adults aged 18 - ≤ 60 primary immunized with two vaccinations with any regimen using any EU marketed SARS-CoV-2 vaccine (mRNA-, vector-, protein-based, attenuated SARS-CoV-2 virus) or with a single application of COVID-19 Vaccine Janssen and subsequently booster immunized with any EU marketed mRNA vaccine
Both cohorts will be assigned to inhaled vaccination with MVA-SARS-2-ST

开始日期2022-02-24

申办/合作机构

Hannover Medical School

[+3]

NCT04895449 / Completed临床1期IIT

A Multi-center Phase Ib Trial to Assess the Safety, Tolerability and Immunogenicity of the Candidate Vaccine MVA-SARS-2-ST in Adults

Multi-center phase Ib study to evaluate the Modified Vaccinia Virus Ankara (MVA) vaccine against SARS-CoV-2 in seronegative (Part A) and previously SARS-CoV-2-vaccinated individuals (Part B).

开始日期2021-07-16

申办/合作机构

Universitätsklinikum Hamburg-Eppendorf

[+5]

EUCTR2021-000548-23-DE / Unknown status临床1/2期IIT

A multi-center, phase Ib trial to assess the safety, tolerability and immunogenicity of the candidate vaccine MVA-SARS-2-ST in adults

开始日期2021-07-07

申办/合作机构

Universitätsklinikum Hamburg-Eppendorf

100 项与 MVA-SARS-2-S 相关的临床结果

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100 项与 MVA-SARS-2-S 相关的转化医学

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100 项与 MVA-SARS-2-S 相关的专利（医药）

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项与 MVA-SARS-2-S 相关的文献（医药）

2023-05-17·Viruses

Short- and Long-Interval Prime-Boost Vaccination with the Candidate Vaccines MVA-SARS-2-ST and MVA-SARS-2-S Induces Comparable Humoral and Cell-Mediated Immunity in Mice.

Article

作者: Schwarz, Jan Hendrik ; Freudenstein, Astrid ; Tscherne, Alina ; Becker, Stephan ; Volz, Asisa ; Sutter, Gerd ; Kalodimou, Georgia ; Jany, Sylvia ; Limpinsel, Leonard ; Kupke, Alexandra ; Rohde, Cornelius

The COVID-19 pandemic caused significant human health and economic consequences. Due to the ability of SARS-CoV-2 to spread rapidly and to cause severe disease and mortality in certain population groups, vaccines are essential for controlling the pandemic in the future. Several licensed vaccines have shown improved protection against SARS-CoV-2 after extended-interval prime-boost immunizations in humans. Therefore, in this study, we aimed to compare the immunogenicity of our two Modified Vaccinia virus Ankara (MVA) based COVID-19 candidate vaccines MVA-SARS-2-S and MVA-SARS-2-ST after short- and long-interval prime-boost immunization schedules in mice. We immunized BALB/c mice using 21-day (short-interval) or 56-day (long-interval) prime-boost vaccination protocols and analyzed spike (S)-specific CD8 T cell immunity and humoral immunity. The two schedules induced robust CD8 T cell responses with no significant differences in their magnitude. Furthermore, both candidate vaccines induced comparable levels of total S, and S2-specific IgG binding antibodies. However, MVA-SARS-2-ST consistently elicited higher amounts of S1-, S receptor binding domain (RBD), and SARS-CoV-2 neutralizing antibodies in both vaccination protocols. Overall, we found very comparable immune responses following short- or long-interval immunization. Thus, our results suggest that the chosen time intervals may not be suitable to observe potential differences in antigen-specific immunity when testing different prime-boost intervals with our candidate vaccines in the mouse model. Despite this, our data clearly showed that MVA-SARS-2-ST induced superior humoral immune responses relative to MVA-SARS-2-S after both immunization schedules.

2023-01-01·Frontiers in cellular and infection microbiology

The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice.

Article

作者: Volz, Asisa ; Willenzon, Stefanie ; Do, Kim Thi Hoang ; Janssen, Anika ; Ristenpart, Jasmin ; Bošnjak, Berislav ; Sutter, Gerd ; Förster, Reinhold

Background and aims:

Modified Vaccinia virus Ankara (MVA) represents a promising vaccine vector for respiratory administration to induce protective lung immunity including tertiary lymphoid structure, the bronchus-associated lymphoid tissue (BALT). However, MVA expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein (MVA-SARS-2-S) required prime-boost administration to induce high titers of anti-Spike antibodies in serum and bronchoalveolar lavage (BAL). As the addition of adjuvants enables efficient tailoring of the immune responses even to live vaccines, we tested whether Toll-like receptor (TLR)-agonists affect immune responses induced by a single dose of intranasally applied MVA-SARS-2-S.

Methods:

We intranasally immunized C57BL/6 mice with MVA-SARS-2-S vaccine in the presence of either TLR3 agonist polyinosinic polycytidylic acid [poly(I:C)], TLR4 agonist bacterial lipopolysaccharide (LPS) from Escherichia coli, or TLR9 agonist CpG oligodeoxynucleotide (CpG ODN) 1826. At different time-points after immunization, we analyzed induced immune responses using flow cytometry, immunofluorescent microscopy, and ELISA.

Results:

TLR agonists had profound effects on MVA-SARS-2-S-induced immune responses. At day 1 post intranasal application, the TLR4 agonist significantly affected MVA-induced activation of dendritic cells (DCs) within the draining bronchial lymph nodes, increasing the ratio of CD11b⁺CD86⁺ to CD103⁺CD86⁺ DCs. Nevertheless, the number of Spike-specific CD8⁺ T cells within the lungs at day 12 after vaccination was increased in mice that received MVA-SARS-2-S co-administered with TLR3 but not TLR4 agonists. TLR9 agonist did neither significantly affect MVA-induced DC activation nor the induction of Spike-specific CD8⁺ T cells but reduced both number and size of bronchus-associated lymphoid tissue. Surprisingly, the addition of all TLR agonists failed to boost the levels of Spike-specific antibodies in serum and bronchoalveolar lavage.

Conclusions:

Our study indicates a potential role of TLR-agonists as a tool to modulate immune responses to live vector vaccines. Particularly TLR3 agonists hold a promise to potentiate MVA-induced cellular immune responses. On the other hand, additional research is necessary to identify optimal combinations of agonists that could enhance MVA-induced humoral responses.

2021-07-13·Proceedings of the National Academy of Sciences of the United States of America1区 · 综合性期刊

Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination

1区 · 综合性期刊

Article

作者: Becker, Stephan ; Sauerhering, Lucie ; Rohde, Cornelius ; Jany, Sylvia ; Liangliang, Nan ; Seilmaier, Michael ; Tscherne, Alina ; Limpinsel, Leonard ; Werner, Anke ; Förster, Reinhold ; Sandrock, Inga ; Freudenstein, Astrid ; Haagmans, Bart L. ; Kupke, Alexandra ; Wendtner, Clemens-Martin ; Sutter, Gerd ; Halwe, Sandro ; Guggemos, Wolfgang ; Odak, Ivan ; Schmidt, Jörg ; Klüver, Michael ; Volz, Asisa ; Gellhorn Serra, Michelle ; Schwarz, Jan Hendrik ; Okba, Nisreen M. A. ; Kalodimou, Georgia ; Brosinski, Katrin ; Bošnjak, Berislav ; Duell, Elke

Significance:

The highly attenuated vaccinia virus MVA is licensed as smallpox vaccine; as a vector it is a component of the approved adenovirus-MVA–based prime-boost vaccine against Ebola virus disease. Here, we provide results from testing the COVID-19 candidate vaccine MVA-SARS-2-S, a poxvirus-based vector vaccine that proceeded to clinical evaluation. When administered by intramuscular inoculation, MVA-SARS-2-S expresses and safely delivers the full-length SARS-CoV-2 S protein, inducing balanced SARS-CoV-2–specific cellular and humoral immunity, and protective efficacy in vaccinated mice. Substantial clinical experience has been gained with MVA vectors using homologous and heterologous prime-boost applications, including the immunization of children and immunocompromised individuals. Thus, MVA-SARS-2-S represents an important resource for developing further optimized COVID-19 vaccines.

100 项与 MVA-SARS-2-S 相关的药物交易

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