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Development of a novel and broadly applicable thermostable bacteriophage VLPs platforms for vaccine design, drug delivery, and imaging

Development of a novel and broadly applicable thermostable bacteriophage VLPs platforms for vaccine design, drug delivery, and imaging
开发新型且广泛适用的热稳定噬菌体 VLP 平台,用于疫苗设计、药物输送和成像
批准号:
10282622
负责人:
Ebenezer Tumban
金额:
$38.93万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-02-24 至 2024-01-31

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英文摘要
PROJECT SUMMARY Virus-like particles (VLPs) resemble - in size, structure, and immunogenicity - the virus from which the coat or envelope protein(s) are derived from except for the fact they lack a viral genome; VLPs are non-infectious and are safe. These features have been exploited to develop VLP-based vaccines against human papillomaviruses and hepatitis B virus; furthermore, coat proteins from ~70 viruses are currently being explored to develop VLP- based vaccines against these viruses. VLPs from some of these viruses have also been used as display platforms to develop chimeric VLPs displaying heterologous peptides from other infectious agents, tumor- associated antigens and other metabolic diseases. The goal of these chimeric VLPs is to induce antibodies against the heterologous antigen displayed on the platforms and not the platforms. In addition to serving as display platforms, VLPs have also been used for targeted delivery of drugs or cargo to specific cancer cells. While the candidate VLPs-based vaccines displaying heterologous peptides are very effective in animal studies, in the majority of studies, VLPs platforms (including adenoviral VLPs or dodecahedron) are derived from viruses that infect humans and in some cases, studies used VLPs platforms that had previously been used to immunize the general population; a good example is HBV vaccine, with a global infant vaccination coverage of 84% in 2015. Vaccines based on some of these platforms, with pre-existing antibodies in the general population, are likely to be less immunogenic in humans. Additionally, there is a limitation on the size of heterologous antigens that can be genetically displayed on some VLPs platforms making it challenging to display a single peptide with multiple epitopes on the same VLPs. Moreover, most of the VLPs platforms are temperature-sensitive making them less suitable in developing countries with poor refrigeration facilities. In this proposal, the PI will develop and characterize novel thermostable bacteriophage VLPs platforms using coat proteins from thermophilic viruses P23-77 and ΦIN93. P23-77 and ΦIN93 was isolated from bacteria that grow at 70-75 °C. Thus VLPs derived from these viruses are likely to be stable at room temperature (RT) or above RT. Additional benefit of these VLPs platforms is that because these viruses do not infect humans, the human population lacks pre-existing neutralizing antibodies against the VLPs platforms; thus, the immunogenicity of the platforms cannot be compromised by pre-existing antibodies. Also, many surface- exposed loops on the capsid may tolerate larger insertions of heterologous antigens. The PI will co-express three coat proteins from P23-77 and two coat proteins from ΦIN93. The PI will assess whether the coat proteins can assemble into VLPs, if they VLPs are thermostable, can tolerate heterologous peptide insertions from human papillomaviruses, and if VLPs are immunogenic in comparison to the virus(es).
期刊论文(4)
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科研奖励(0)
会议论文
DOI: 10.3390/v15051109
发表时间: 2023-05-02
期刊: Viruses
影响因子: --
作者: [Kheirvari M, Liu H, Tumban E]
通讯作者: Tumban E
DOI: 10.1016/j.pep.2021.105932
发表时间: 2021-11
期刊: Protein expression and purification
影响因子: 1.6
作者: [Zhai L, Anderson D, Bruckner E, Tumban E]
通讯作者: Tumban E
Bacteriophage Virus-Like Particles: Platforms for Vaccine Design.
噬菌体病毒样颗粒:疫苗设计平台。
DOI: 10.1007/978-1-0716-3549-0_24
发表时间: 2024
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
作者: [Tumban,Ebenezer]
通讯作者: Tumban,Ebenezer
DOI: 10.3390/ijms24098222
发表时间: 2023-05-04
期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
影响因子: 5.6
作者: [Liu, Hong, Kheirvari, Milad, Tumban, Ebenezer]
通讯作者: Tumban, Ebenezer
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