更新于：2024-11-01

M2 protein x TLR5

更新于：2024-11-01

基本信息

关联

项与 M2 protein x TLR5 相关的药物

VAX-102

靶点

M2 protein x TLR5

作用机制

M2 protein抑制剂 [+1]

在研机构

VaxInnate Corp.

原研机构

VaxInnate Corp.

在研适应症

甲型流感病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 M2 protein x TLR5 相关的临床试验

NCT00921947 / Completed临床1/2期

A Phase II, Randomized, Open-Label Study to Evaluate the Comparative Safety and Immunogenicity of 1.0 µg Intramuscular (i.m.) and 2.0 µg Subcutaneous (s.c.) Dosing With VAX102 (M2e-flagellin) in Healthy Adults

To assess the safety, reactogenicity, tolerability, and adverse events (AEs) of the VAX102 vaccine in a two dose regimen (Day 0 and Day 28) at the 1.0 µg dose level delivered i.m., or the 2.0 µg dose level delivered s.c. in a healthy adult population.
To assess the immunogenicity (anti-M2e serum antibody concentration) of the VAX102 vaccine in a two dose regimen (Day 0 and Day 28) at the 1.0 µg dose level delivered i.m., or the 2.0 µg dose level delivered s.c. as measured by an enzyme-linked immunosorbent assay (ELISA) in a healthy adult population.

开始日期2009-06-01

申办/合作机构

VaxInnate Corp.

NCT00921973 / Completed临床1期

A Multicenter, Double-Blinded, Randomized, Placebo Controlled Study to Investigate the Safety and Immunogenicity of VAX102 When Given in the Same Arm With the Standard Influenza Vaccine in Healthy Adults

The study will assess the safety, reactogenicity, and tolerability of VAX102 when given with Trivalent Inactivated Influenza Vaccine (TIV) delivered in the same arm as two separate IM injections in healthy adults 18 to 49 years. The investigators will measure the immunogenicity of the VAX102 when given with TIV and the antibody response to TIV when given with VAX102 compared to TIV alone.

开始日期2009-06-01

申办/合作机构

VaxInnate Corp.

NCT00921206 / Completed临床1期

Open-label Study to Investigate the Humoral and Cellular Immune Response to Two Doses of VAX102 Influenza Vaccine in Healthy Adults

The objective is to assess the humoral and cellular immune response of the VAX102 vaccine delivered IM and SC in a prime-boost regimen at dose levels 1 µg or 2 µg in healthy adults against the influenza A virus M2e antigen after each vaccination.

开始日期2009-06-01

申办/合作机构

VaxInnate Corp.

[+1]

100 项与 M2 protein x TLR5 相关的临床结果

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100 项与 M2 protein x TLR5 相关的转化医学

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0 项与 M2 protein x TLR5 相关的专利（医药）

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项与 M2 protein x TLR5 相关的文献（医药）

2016-03-01·Vaccine3区 · 医学

Recombinant M2e outer membrane vesicle vaccines protect against lethal influenza A challenge in BALB/c mice

3区 · 医学

Article

作者: Leifer, Cynthia A ; Putnam, David ; Watkins, Hannah C ; Guarino, Cassandra M ; DeLisa, Matthew P ; Rappazzo, C Garrett ; Lopez, Jody L ; Chau, Annie ; Whittaker, Gary R

Currently approved influenza vaccines predominantly protect through antibodies directed against the highly variable glycoprotein hemagglutinin (HA), necessitating annual redesign and formulation based on epidemiological prediction of predominant circulating strains. More conserved influenza protein sequences, such as the ectodomain of the influenza M2 protein, or M2e, show promise as a component of a universal influenza A vaccine, but require a Th1-biased immune response for activity. Recently, recombinant, bacterially derived outer membrane vesicles (OMVs) demonstrated potential as a platform to promote a Th1-biased immune response to subunit antigens. Here, we engineer three M2e-OMV vaccines and show that all elicit strong IgG titers, with high IgG2a:IgG1 ratios, in BALB/c mice. Additionally, the administration of one M2e-OMV construct containing tandem heterologous M2e peptides (M2e4xHet-OMV) resulted in 100% survival against lethal doses of the mouse-adapted H1N1 influenza strain PR8. Passive transfer of antibodies from M2e4xHet-OMV vaccinated mice to unvaccinated mice also resulted in 100% survival to challenge, indicating that protection is driven largely via antibody-mediated immunity. The potential mechanism through which M2e-OMVs initiated the immune response was explored and it was found that the constructs triggered TLR1/2, TLR4, and TLR5. Our data indicate that OMVs have potential as a platform for influenza A vaccine development due to their unique adjuvant profile and intrinsic pathogen-mimetic nature.

2015-12-01·BMC Biotechnology4区 · 工程技术

Rapid high-yield expression of a candidate influenza vaccine based on the ectodomain of M2 protein linked to flagellin in plants using viral vectors

4区 · 工程技术

ArticleOA

作者: Ravin, Nikolai V ; Tsybalova, Liudmila M ; Kuprianov, Victor V ; Mardanova, Eugenia S ; Stepanova, Liudmila A ; Lomonosoff, George P ; Kotlyarov, Roman Y

BACKGROUNDThe extracellular domain of matrix protein 2 (M2e) of influenza A virus is a promising target for the development of a universal vaccine against influenza because M2e sequences are highly conserved among human influenza A strains. However, native M2e is poorly immunogenic, but its immunogenicity can be increased by delivery in combination with adjuvants or carrier particles. It was previously shown that fusion of M2e to bacterial flagellin, the ligand for Toll-like receptor (TLR) 5 and powerful mucosal adjuvant, significantly increases the immunogenicity and protective capacity of M2e.RESULTSIn this study, we report for the first time the transient expression in plants of a recombinant protein Flg-4M comprising flagellin of Salmonella typhimurium fused to four tandem copies of the M2e peptide. The chimeric construct was expressed in Nicotiana benthamiana plants using either the self-replicating potato virus X (PVX) based vector, pA7248AMV-GFP, or the cowpea mosaic virus (CPMV)-derived expression vector, pEAQ-HT. The highest expression level up to 30% of total soluble protein (about 1 mg/g of fresh leaf tissue) was achieved with the PVX-based expression system. Intranasal immunization of mice with purified Flg-4M protein induced high levels of M2e-specific serum antibodies and provided protection against lethal challenge with influenza virus.CONCLUSIONSThis study confirms the usefulness of flagellin as a carrier of M2e and its relevance for the production of M2e-based candidate influenza vaccines in plants.

2012-08-01·Clinical and Vaccine Immunology

Enhanced Influenza Virus-Like Particle Vaccines Containing the Extracellular Domain of Matrix Protein 2 and a Toll-Like Receptor Ligand

Article

作者: Ying Chun Wang ; Richard W. Compans ; Bao Zhong Wang ; Harvinder S. Gill ; Elena V. Vassilieva ; Sang Moo Kang ; Li Wang

ABSTRACTThe extracellular domain of matrix protein 2 (M2e) is conserved among influenza A viruses. The goal of this project is to develop enhanced influenza vaccines with broad protective efficacy using the M2e antigen. We designed a membrane-anchored fusion protein by replacing the hyperimmunogenic region ofSalmonella entericaserovar Typhimurium flagellin (FliC) with four repeats of M2e (4.M2e-tFliC) and fusing it to a membrane anchor from influenza virus hemagglutinin (HA). The fusion protein was incorporated into influenza virus M1-based virus-like particles (VLPs). These VLPs retained Toll-like receptor 5 (TLR5) agonist activity comparable to that of soluble FliC. Mice immunized with the VLPs by either intramuscular or intranasal immunization showed high levels of systemic M2-specific antibody responses compared to the responses to soluble 4.M2e protein. High mucosal antibody titers were also induced in intranasally immunized mice. All intranasally immunized mice survived lethal challenges with live virus, while intramuscularly immunized mice showed only partial protection, revealing better protection by the intranasal route. These results indicate that a combination of M2e antigens and TLR ligand adjuvants in VLPs has potential for development of a broadly protective influenza A virus vaccine.