Yun Jin-Seung, Shin Eunkyung, Lee Young-Ran, Lee Jung-Ah, Lee Hyeokjin, Kim Jong-Seok, Shin Sung Jae, Ha Sang-Jun, Lee Sang-Won, Kim Dokeun, Yoo Jung-Sik, Jeong Hye-Sook
Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Front Microbiol. 2025 Jan 24;16:1492268. doi: 10.3389/fmicb.2025.1492268. eCollection 2025.
The inadequate efficacy of the Bacillus Calmette-Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against .
We constructed a multi-antigenic recombinant Ad5 vectored vaccine expressing four antigens (Ag85B-ESAT6-MPT64-Rv2660c) of (rAd-TB4), immunized with rAd-TB4 (5 × 10 infectious virus units/mouse) twice at an interval of 4 weeks starting at 10 weeks after BCG priming, and evaluated its boosting efficacy in a BCG-primed mouse model, and determined the optimal immunization route.
Compared with the BCG-only (2 × 10 colony forming units/mouse), subcutaneous injection of rAd-TB4 (1 × 10 infectious virus units/mL; two doses) elicited a T-cell response and cytokine production in lung lymphocytes and splenocytes. rAd-TB4 immunization significantly reduced bacterial loads and inflamed lung areas compared to BCG immunization ( < 0.01) and protected against the H37Rv challenge performed at 17 weeks of BCG priming. RNA sequencing of the whole blood of rAd-TB4-vaccinated mice collected pre- and, 1 and 4 weeks post-infection, identified differentially expressed genes associated with immune and inflammatory responses, especially those in the Wnt signaling pathway.
Our results indicate that rAd-TB4 immunization enhances the immune response to the vaccine boosting antigens in BCG-primed mice, making it a potential adult pulmonary TB vaccine candidate.
卡介苗（BCG）对成人肺结核（TB）的疗效不足，因此需要研发新的有效疫苗。能诱导T细胞反应的人5型腺病毒（Ad5）是一种广泛使用的病毒载体。在本研究中，我们旨在评估一种多抗原重组Ad5载体疫苗的疗效，并确定增强针对……的免疫反应的最佳免疫途径。
我们构建了一种表达四种结核杆菌抗原（Ag85B-ESAT6-MPT64-Rv2660c）的多抗原重组Ad5载体疫苗（rAd-TB4），在卡介苗初免10周后，以4周的间隔用rAd-TB4（5×10个感染性病毒单位/小鼠）免疫两次，并在卡介苗初免的小鼠模型中评估其增强疗效，同时确定最佳免疫途径。
与仅接种卡介苗（2×10个菌落形成单位/小鼠）相比，皮下注射rAd-TB4（1×10个感染性病毒单位/毫升；两剂）可诱导肺淋巴细胞和脾细胞产生T细胞反应和细胞因子。与卡介苗免疫相比，rAd-TB4免疫显著降低了细菌载量和肺部炎症区域（P<0.01），并在卡介苗初免17周时抵御了H37Rv攻击。对rAd-TB4疫苗接种小鼠在感染前、感染后1周和4周采集的全血进行RNA测序，确定了与免疫和炎症反应相关的差异表达基因，尤其是Wnt信号通路中的基因。
我们的结果表明，rAd-TB4免疫增强了卡介苗初免小鼠对疫苗增强抗原的免疫反应，使其成为一种潜在的成人肺结核疫苗候选物。
