Kurtz Sherry L, Gould Victoria, Flores-Valdez Mario A, Elkins Karen L
Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Vaccine. 2025 Aug 13;61:127347. doi: 10.1016/j.vaccine.2025.127347. Epub 2025 Jun 3.
Mycobacterium tuberculosis remains a global health threat despite the world-wise use of the vaccine Bacille Calmette Guerin (BCG). Introducing a new vaccine could help to combat this pandemic, and efforts are underway to develop novel candidates, including by modifying parental BCG. Here, we use the genetically and phenotypically heterogenous Diversity Outbred mice to test the efficacy of the novel vaccine candidate BCGΔBCG1419c. BCGΔBCG1419c contains a mutation in BCG1419c, a phosphodiesterase linked with biofilm formation. BCGΔBCG1419c was previously shown to be more attenuated than the parental BCG strain in inbred mice and to provide protection against aerogenic M. tuberculosis challenge in inbred mice and guinea pigs. In the current study, we find that protection afforded by BCGΔBCG1419c in outbred DO mice is at least equivalent to, if not better than, that provided by parental BCG.
尽管卡介苗（BCG）在全球范围内广泛使用，但结核分枝杆菌仍然是全球健康的一大威胁。引入一种新疫苗可能有助于对抗这一流行病，目前正在努力开发新型候选疫苗，包括对亲本卡介苗进行改造。在这里，我们使用基因和表型均具有异质性的多样性远交系小鼠来测试新型候选疫苗BCGΔBCG1419c的疗效。BCGΔBCG1419c在与生物膜形成相关的磷酸二酯酶BCG1419c中存在突变。先前研究表明，BCGΔBCG1419c在近交系小鼠中比亲本卡介苗菌株的毒力更低，并且能为近交系小鼠和豚鼠提供针对空气传播的结核分枝杆菌攻击的保护。在当前研究中，我们发现BCGΔBCG1419c在远交系DO小鼠中提供的保护作用即使不比亲本卡介苗更好，至少也是相当的。
