一个Plasmodium vivaxDuffy结合蛋白免疫原的基于结构的设计将抗体对功能表位素的反应集中在功能表位素上
Thayne H Dickey1, Holly McAleese2, Nichole D Salinas1
1Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Protein science : a publication of the Protein Society
|July 11, 2024
概括
一种新的疟疾疫苗抗原,达菲结合蛋白II区域 (DBP-II),被设计为集中免疫反应. 这种稳定碎片会产生抗体,对抗生素Plasmodium vivax.具有增强的阻断活性.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗开发 疫苗开发
- 结构生物学 结构生物学
背景情况:
- 达菲结合蛋白 (DBP) 是疟疾疫苗针对Plasmodium vivax的一个关键目标.
- 本地DBP II区域 (DBP-II) 产生抗体,但这些抗体并不总是有效地阻止红细胞入侵.
研究的目的:
- 为了设计一个稳定的DBP-II免疫原,将免疫反应引导到受体结合表面.
- 加强中和抗体的开发,以获得更有效的疟疾疫苗.
主要方法:
- 基于结构的计算设计被用来创建一个截断的DBP-II (S1S2子域).
- 引入了氨基酸替代物以稳定S1S2片段,同时保留关键表位.
- 工程抗原的免疫性和抗体配置文件在小鼠中进行了评估.
主要成果:
- 工程S1S2免疫原被稳定,而不会影响中和表位.
- 用S1S2免疫原免疫接种产生了DBP-II特异性抗体.
- 与原生DBP-II相比,由工程抗原引起的抗体显示出明显丰富的阻断活性.
结论:
- 一种可通用的蛋白质设计策略可以稳定核心碎片并集中免疫反应.
- 经过工程设计的DBP-II S1S2免疫原代表了疟疾疫苗开发的有希望的候选人.
- 这种方法可以通过向关键的功能表位素来提高疫苗的疗效.
相关概念视频
01:10Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
01:10Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
01:26Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:28Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...