Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2024 Oct 4;386(6717):69-75. doi: 10.1126/science.adn4955. Epub 2024 Oct 3.
infection (CDI) is an urgent public health threat with limited preventative options. In this work, we developed a messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine targeting toxins and virulence factors. This multivalent vaccine elicited robust and long-lived systemic and mucosal antigen-specific humoral and cellular immune responses across animal models, independent of changes to the intestinal microbiota. Vaccination protected mice from lethal CDI in both primary and recurrent infection models, and inclusion of non-toxin cellular and spore antigens improved decolonization of toxigenic from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel therapeutics with potential for limiting acute disease and promoting bacterial decolonization.
感染（CDI）是一种紧迫的公共健康威胁，预防选择有限。在这项工作中，我们开发了一种针对毒素和毒力因子的信使 RNA（mRNA）-脂质纳米颗粒（LNP）疫苗。这种多价疫苗在动物模型中引发了强大且持久的全身和粘膜抗原特异性体液和细胞免疫反应，而与肠道微生物群的变化无关。疫苗接种可在原发性和复发性感染模型中保护小鼠免受致命的 CDI，并且包含非毒性细胞和孢子抗原可改善从胃肠道中消除产毒 。我们的研究表明，mRNA-LNP 疫苗技术是开发新型 治疗方法的有前途的平台，具有限制急性疾病和促进细菌去定植的潜力。
