Kumari Sneha, Martinez-Garcia Jonathan, Ehrman Ryanne Nicole, Tang Wendy, Miles Joshua, Basak Priyanka, Howlett Thomas Sinclair, Wijesundara Yalini Hansika, Wang Ziqi, Izzo Angelo, Restrepo Blanca, Lu Lenette, Meloni Gabriele, Gassensmith Jeremiah J
Department of Chemistry and Biochemistry, University of Texas at Dallas, Richardson, Texas 75080, United States.
Department of Immunology, UT Southwestern Medical Center, Dallas, Texas 75390, United States.
ACS Infect Dis. 2025 Jan 10;11(1):204-215. doi: 10.1021/acsinfecdis.4c00771. Epub 2024 Dec 11.
Tuberculosis is one of the deadliest infectious diseases and continues to be a major health risk in many parts of the world. Even today, the century-old Bacillus Calmette-Guerin (BCG) vaccine is the only formulation on the market and is ineffective for several sections of the global population responsible for transmission. In the search for antigens that can mount a robust immune response, we have reported the recombinant expression and purification of two novel membrane proteins, the Cation transporter protein V (CtpV) and the Mycobacterial copper transporter B (MctB) present on the membrane surface of . CtpV was tested as an antigen against the plasma of tuberculosis patients and was found to have a unique immune response profile compared with more commonly studied tuberculosis (TB) antigens. CtpV and MctB were reconstituted into proteoliposomes─individually and in combination─to stabilize them in a lipid bilayer and create a nanoparticle vaccine platform. experiments demonstrated that when delivered with an adjuvant, these antigens generated a robust Th1-biased T-cell response in mice, with the combination of both antigens performing the best and generating a response comparable to BCG. Since tuberculosis vaccines often need to be shipped to areas with fluctuating power supply, we encapsulated the proteoliposomes and the adjuvant in ZIF-8 to create a shelf-stable formulation. Complementary studies were carried out to confirm that the ZIF-8 coating did not interfere with or compromise the immunogenicity of the antigens.
结核病是最致命的传染病之一，在世界许多地区仍然是重大的健康风险。即使在今天，有百年历史的卡介苗（BCG）仍是市场上唯一的制剂，对全球人口中负责传播的几个群体无效。在寻找能够引发强大免疫反应的抗原过程中，我们报道了两种新型膜蛋白的重组表达和纯化，即存在于[具体细菌名称未给出]膜表面的阳离子转运蛋白V（CtpV）和分枝杆菌铜转运蛋白B（MctB）。CtpV作为针对结核病患者血浆的抗原进行了测试，结果发现与更常研究的结核病（TB）抗原相比，它具有独特的免疫反应谱。CtpV和MctB被单独或组合重构成蛋白脂质体，以使其在脂质双层中稳定，并创建一个纳米颗粒疫苗平台。实验表明，当与佐剂一起递送时，这些抗原在小鼠体内产生了强大的以Th1为主的T细胞反应，两种抗原组合的效果最佳，产生的反应与卡介苗相当。由于结核病疫苗通常需要运往电力供应不稳定的地区，我们将蛋白脂质体和佐剂封装在ZIF-8中，以创建一种货架稳定的制剂。进行了补充研究以确认ZIF-8包衣不会干扰或损害抗原的免疫原性。
