Huang Ting, Che Siyou, Lv Zheng, Hao Danrui, Wang Runyu, Yi Qinxuan, Mei Ling, Yuan Yang, Zou Hang, Guo Yidong, Wang Xinrong, Chu Yiwen, Zhao Kelei
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, China.
Engineering Research Center for Pharmaceuticals and Equipments of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, China.
mSphere. 2025 Jan 28;10(1):e0077524. doi: 10.1128/msphere.00775-24. Epub 2024 Dec 31.
is a prominent Gram-negative and encapsulated opportunistic pathogen that causes a multitude of infections such as severe respiratory and healthcare-associated infections. Despite the widespread anti-microbial resistance and the high mortality rate, currently, no clinically vaccine is approved for battling . To date, messenger RNA (mRNA) vaccine is one of the most advancing technologies and are extensively investigated for viral infection, while infrequently applied for prevention of bacterial infections. In the present study, we aim to construct a new mRNA vaccine encoding YidR or combining with a tissue plasminogen activator signal sequence for preventing infection. Adaptive immunity was determined in mRNA vaccines-immunized mice and the protective effects of mRNA vaccines were evaluated in infected models. The results showed that lipid nanoparticle (LNP)-YidR-mRNA vaccine was produced with good morphology, high the encapsulation efficiency, and the specific antigen was highly expressed in cells . In addition, immunization with either LNP-YidR or LNP-YidR-SP elicited a Th1-biased immune response, reduced bacterial load, and provided broad protection in the lung infection models. Importantly, the LNP-YidR-SP mRNA vaccine induced strong adaptive humoral and cellular immunity and increased the survivability of mice compared to the other groups. Our findings serve as a focal point for developing a potential mRNA vaccine against , indicating the potential of mRNA vaccines for improving next-generation bacterial vaccine.IMPORTANCE is a notorious and clinical bacterium that is evolving in community-acquired and nosocomial settings. This opportunistic pathogen causes severe infectious diseases, including urinary tract infection and pneumonia, and causes a concerning global public burden. Despite efforts having been created to develop different types of vaccines, there is no licensed vaccine for preventing infection. Therefore, to develop an effective tactic is essential to combat -caused diseases. This study provides a novel vaccine strategy against and a potent platform to elicit high levels of humoral and cell-meditated immunity.
是一种显著的革兰氏阴性且有荚膜的机会性病原体，可引发多种感染，如严重的呼吸道感染和医疗保健相关感染。尽管存在广泛的抗菌耐药性和高死亡率，但目前尚无临床批准的用于对抗的疫苗。迄今为止，信使核糖核酸（mRNA）疫苗是最先进的技术之一，已被广泛研究用于病毒感染，而很少用于预防细菌感染。在本研究中，我们旨在构建一种编码YidR或与组织纤溶酶原激活剂信号序列结合的新型mRNA疫苗，以预防感染。在mRNA疫苗免疫的小鼠中测定适应性免疫，并在感染模型中评估mRNA疫苗的保护作用。结果表明，脂质纳米颗粒（LNP）-YidR-mRNA疫苗形态良好，包封效率高，特异性抗原在细胞中高表达。此外，用LNP-YidR或LNP-YidR-SP免疫可引发以Th1为主的免疫反应，降低细菌载量，并在肺部感染模型中提供广泛的保护。重要的是，与其他组相比，LNP-YidR-SP mRNA疫苗诱导了强烈的适应性体液和细胞免疫，并提高了小鼠的存活率。我们的发现为开发一种潜在的抗mRNA疫苗提供了重点，表明mRNA疫苗在改进下一代细菌疫苗方面的潜力。重要性是一种臭名昭著的临床细菌，正在社区获得性和医院环境中演变。这种机会性病原体可导致严重的传染病，包括尿路感染和肺炎，并造成令人担忧的全球公共负担。尽管已努力开发不同类型的疫苗，但尚无预防感染的许可疫苗。因此，制定有效的策略对于对抗引起的疾病至关重要。本研究提供了一种针对的新型疫苗策略和一个引发高水平体液和细胞介导免疫的有效平台。
