
School of Medicine Publications and Presentations
Testing the Antigenic Potential of Transmembrane Proteins To Develop a Thermostable Tuberculosis MOF-Liposomal Vaccine
Document Type
Article
Publication Date
1-2025
Abstract
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 Mycobacterium tuberculosis. 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. In vivo 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 in vivo studies were carried out to confirm that the ZIF-8 coating did not interfere with or compromise the immunogenicity of the antigens.
Recommended Citation
Kumari, S., Martinez-Garcia, J., Ehrman, R. N., Tang, W., Miles, J., Basak, P., Howlett, T. S., Wijesundara, Y. H., Wang, Z., Izzo, A., Restrepo, B., Lu, L., Meloni, G., & Gassensmith, J. J. (2025). Testing the Antigenic Potential of Transmembrane Proteins To Develop a Thermostable Tuberculosis MOF-Liposomal Vaccine. ACS infectious diseases, 11(1), 204–215. https://doi.org/10.1021/acsinfecdis.4c00771
Publication Title
ACS infectious diseases
DOI
https://doi.org/10.1021/acsinfecdis.4c00771
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© XXXX American Chemical Society