Kwon Kee Woong, Kang Tae Gun, Lee Ara, Jin Seung Mo, Lim Yong Taik, Shin Sung Jae, Ha Sang-Jun
Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea.
Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul 03722, Korea.
Immune Netw. 2023 Feb 16;23(2):e16. doi: 10.4110/in.2023.23.e16. eCollection 2023 Apr.
Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against (Mtb) infection by directing Th1-biased CD4 T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.
卡介苗（BCG）是唯一获得许可用于预防结核病（TB）的疫苗。此前，我们的研究小组通过引导肺中共同表达干扰素-γ、肿瘤坏死因子-α和白细胞介素-2的Th1偏向性CD4 T细胞，证明了Rv0351和Rv3628对结核分枝杆菌（Mtb）感染的疫苗潜力。在此，我们评估了在卡介苗初免的小鼠中，以不同佐剂配制的组合抗原（Rv0351/Rv3628）作为亚单位加强疫苗针对高毒力临床结核分枝杆菌菌株K（Mtb K）的免疫原性和疫苗潜力。与仅接种卡介苗或仅接种亚单位疫苗相比，卡介苗初免和亚单位加强免疫方案表现出显著增强的Th1反应。接下来，我们评估了与四种不同类型的基于单磷酰脂质A（MPL）的佐剂配制时组合抗原的免疫原性：1）脂质体形式的二甲基二十八烷基溴化铵（DDA）、MPL和海藻糖二分枝菌酸酯（TDM）（DMT），2）脂质体形式的MPL和聚肌苷酸:聚胞苷酸（Poly I:C）（MP），3）脂质体形式的MPL、Poly I:C和QS21（MPQ），以及4）角鲨烯乳剂形式的MPL和Poly I:C（MPS）。MPQ和MPS在诱导Th1方面比DMT或MP表现出更强的佐剂活性。特别是，在结核病慢性期，与仅接种卡介苗的疫苗相比，卡介苗初免和亚单位-MPS加强免疫方案显著降低了针对Mtb K感染的细菌载量和肺部炎症。总体而言，我们的研究结果突出了佐剂成分和配方对于诱导具有最佳Th1反应的增强保护的重要性。
