Pongma Chitsuda, Keawvilai Pornlapat, Pattarakankul Thitiporn, Rotcheewaphan Suwatchareeporn, Alameh Mohamad-Gabriel, Prompetchara Eakachai, Premchaiporn Pornpimol, Chareanpat Promchat, Yindeeyoungyeon Wandee, Heyes James, Lam Kieu, Ruxrungtham Kiat, Palaga Tanapat
Graduate Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; Center of Excellence in Vaccine Research and Development (Chula Vaccine Research, Center-Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Biochem Biophys Res Commun. 2025 Sep 8;778:152408. doi: 10.1016/j.bbrc.2025.152408. Epub 2025 Jul 25.
The mRNA vaccine platform holds a great promise as novel tuberculosis vaccine. In this study, the use of mRNA encoding Ag85B from M. tuberculosis (M. tb) formulated in lipid nanoparticle (LNP) was investigated as a standalone vaccine or a booster dose for BCG in mice. Two doses of Ag85 B mRNA/LNP induced robust specific humoral response and Th1 response as measured by IFN-γ-producing T cells and polyfunctional CD8 T cells (IFN-γ, TNF-α, and IL-2) in spleens and lungs. A heterologous BCG prime and mRNA/LNP boost regimen induced higher response to broad M. tb antigens than one dose of BCG vaccine or homologous prime-boost regimen by mRNA/LNP. This approach produced the highest IFN-γ-producing T cells and polyfunctional CD4 T cells, indicating that mRNA/LNP provided help that enhanced the response to other antigens beyond Ag85B. The mycobacterial growth inhibition assay showed that the heterologous prime boost effectively reduced mycobacterial growth to the lowest level among the groups tested in this study. Thus, by integrating the mRNA vaccine platform into the tuberculosis vaccine development, it may be possible to provide an effective strategy to control tuberculosis.
mRNA疫苗平台作为新型结核病疫苗具有巨大潜力。在本研究中，对脂质纳米颗粒（LNP）中配制的编码结核分枝杆菌（M. tb）Ag85B的mRNA作为小鼠的单一疫苗或卡介苗（BCG）加强剂量进行了研究。两剂Ag85B mRNA/LNP诱导了强烈的特异性体液反应和Th1反应，通过脾脏和肺中产生IFN-γ的T细胞和多功能CD8 T细胞（IFN-γ、TNF-α和IL-2）进行测量。与一剂BCG疫苗或mRNA/LNP的同源初免-加强方案相比，异源BCG初免和mRNA/LNP加强方案对广泛的结核分枝杆菌抗原诱导了更高的反应。这种方法产生了最高数量的产生IFN-γ的T细胞和多功能CD4 T细胞，表明mRNA/LNP提供了帮助，增强了对Ag85B以外其他抗原的反应。分枝杆菌生长抑制试验表明，异源初免-加强在本研究测试的组中有效地将分枝杆菌生长降低到最低水平。因此，通过将mRNA疫苗平台整合到结核病疫苗开发中，有可能提供一种控制结核病的有效策略。
