Baliban Scott M, Shridhar Surekha, Luo Kun, Kolasny Jacqueline, Hyun Sang, Zhao Zhiyong, Tennant Sharon M, Cross Alan S
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Infect Dis. 2025 Jul 30;232(1):133-142. doi: 10.1093/infdis/jiae641.
Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A in addition to gastroenteritis and invasive disease, predominantly attributable to nontyphoidal Salmonella serovars Typhimurium and Enteritidis, are major causes of death and disability across the globe. A broad-spectrum vaccine that protects against disease caused by typhoidal and nontyphoidal serovars of Salmonella is not available for humans but would prevent a considerable burden of disease worldwide.
We previously developed a broad-spectrum vaccine for gram-negative bacteria that is based on the inner core domain of detoxified Escherichia coli O111, Rc (J5) mutant lipooligosaccharide, a highly conserved antigen across gram-negative bacteria, complexed with an outer membrane protein of group B Neisseria meningitidis. In this study, mice and rabbits were immunized with the J5 core/outer membrane protein subunit vaccine. We assessed the cross-reactivity of antisera with various Salmonella species lipopolysaccharides and the protective efficacy of passive and active immunization with J5 vaccine against experimental nontyphoidal Salmonella infection in mice.
Vaccination with J5 induced IgG responses that strongly recognized lipopolysaccharide from both typhoidal and nontyphoidal Salmonella and imparted a survival benefit against lethal heterologous challenges with S. Typhimurium and S. Enteritidis. Additionally, passive transfer studies with rabbit hyperimmune sera raised against the J5 vaccine revealed that anti-core antibodies were protective against lipopolysaccharide challenge in D-galactosamine-sensitized mice.
Our findings support the development of core glycolipids as a novel Salmonella vaccine candidate. Further investigation is warranted to determine the efficacy of the J5 core/outer membrane protein vaccine against other Salmonella serovars of concern.
由伤寒沙门氏菌和甲型副伤寒沙门氏菌引起的肠热症，以及主要由非伤寒沙门氏菌血清型鼠伤寒沙门氏菌和肠炎沙门氏菌引起的肠胃炎和侵袭性疾病，是全球死亡和残疾的主要原因。目前尚无一种能预防伤寒和非伤寒沙门氏菌血清型引起疾病的广谱疫苗，但这种疫苗可预防全球范围内相当大的疾病负担。
我们之前开发了一种针对革兰氏阴性菌的广谱疫苗，该疫苗基于解毒的大肠杆菌O111、Rc（J5）突变体脂寡糖的内核结构域，这是一种革兰氏阴性菌中高度保守的抗原，与B群脑膜炎奈瑟菌的外膜蛋白复合而成。在本研究中，用J5核心/外膜蛋白亚单位疫苗对小鼠和兔子进行免疫。我们评估了抗血清与各种沙门氏菌脂多糖的交叉反应性，以及J5疫苗被动和主动免疫对小鼠实验性非伤寒沙门氏菌感染的保护效果。
用J5疫苗接种可诱导IgG反应，该反应能强烈识别伤寒和非伤寒沙门氏菌的脂多糖，并赋予对鼠伤寒沙门氏菌和肠炎沙门氏菌致死性异源攻击的生存优势。此外，用针对J5疫苗产生的兔超免疫血清进行的被动转移研究表明，抗核心抗体对D - 半乳糖胺致敏小鼠的脂多糖攻击具有保护作用。
我们的研究结果支持将核心糖脂作为一种新型沙门氏菌疫苗候选物进行开发。有必要进一步研究以确定J5核心/外膜蛋白疫苗对其他相关沙门氏菌血清型的疗效。
