Janardhanan Jeshina, Wagh Chanchal, Yang Jibing, Charles Richelle C, Pansuriya Ruchir Kumar, Chowdhury Fahima, Kaminski Robert W, Khan Ashraful Islam, Bhuiyan Taufiqur Rahman, Qadri Firdausi, Kováč Pavol, Xu Peng, Ryan Edward T
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.
Center for Comparative Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Am J Trop Med Hyg. 2025 Aug 5. doi: 10.4269/ajtmh.25-0269.
Shigella infection is a major cause of diarrhea, cognitive and physical stunting, and death in young children in resource-limited settings. A vaccine that is protective against shigellosis is needed. Immune responses that target the O-specific polysaccharide (OSP) of Shigella spp. are protective against shigellosis. We previously reported the development and evaluation of a conjugate vaccine targeting Shigella flexneri (S. flexneri) 3a in mice. Here, we report the evaluation of this vaccine (Shigella conjugate vaccine S. flexneri 3a OSP conjugated to a 52 kiloDalton recombinant fragment of the tetanus toxin heavy chain [SCV-Sf3a OSP:rTTHc]) in a second animal model: the guinea pig. This vaccine induced prominent OSP-, lipopolysaccharide-, and rTTHc-specific Immunoglobulin (Ig)G, IgA, and IgM responses in the sera of vaccinated animals. Shigella conjugate vaccine S. flexneri 3a also induced serum bactericidal functional antibody responses, and vaccinated guinea pigs were protected against a virulent strain of keratoconjunctival challenge in the standard Shigella Sereny assay. These results support the further development of SCV-Sf3a OSP:rTTHc.
志贺氏菌感染是资源有限地区幼儿腹泻、认知和身体发育迟缓以及死亡的主要原因。需要一种预防志贺氏菌病的疫苗。针对志贺氏菌属O特异性多糖（OSP）的免疫反应可预防志贺氏菌病。我们之前报道了在小鼠中开发和评估针对福氏志贺菌（S. flexneri）3a的结合疫苗。在此，我们报告在第二种动物模型——豚鼠中对该疫苗（福氏志贺菌3a OSP与破伤风毒素重链的52千道尔顿重组片段结合的志贺氏菌结合疫苗[SCV-Sf3a OSP:rTTHc]）的评估。该疫苗在接种动物血清中诱导了显著的OSP、脂多糖和rTTHc特异性免疫球蛋白（Ig）G、IgA和IgM反应。福氏志贺菌3a志贺氏菌结合疫苗还诱导了血清杀菌功能抗体反应，并且在标准志贺氏菌塞雷尼试验中，接种疫苗的豚鼠对角膜结膜攻击的强毒株具有保护作用。这些结果支持进一步开发SCV-Sf3a OSP:rTTHc。
