Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS Negl Trop Dis. 2014 Feb 6;8(2):e2683. doi: 10.1371/journal.pntd.0002683. eCollection 2014 Feb.
Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children.
Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide-core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli.
We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model.
We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens.
针对霍乱的保护性免疫具有血清群特异性。霍乱弧菌的血清群特异性由脂多糖（LPS）的 O 特异性多糖（OSP）决定。通常情况下，多糖的免疫原性较差，尤其是在幼儿中。
在这里，我们报告了一种霍乱结合疫苗（OSP:TThc）在小鼠中的评估结果，该疫苗由霍乱弧菌 O1 型 Ogawa O 型特异性多糖核心（OSP）和重组破伤风类毒素重链片段（TThc）制成。我们在第 0、21 和 42 天通过肌肉注射 OSP:TThc 或仅 OSP，或添加非毒性免疫佐剂 dmLT（源自大肠杆菌不耐热毒素的热不稳定毒素）对小鼠进行免疫。
我们在接受 OSP:TThc 佐剂或无佐剂的小鼠中单次免疫后检测到针对 OSP 的显著血清 IgG 抗体反应。在这些队列的第二次免疫后检测到针对 LPS 的 IgG 反应。在接受未结合 OSP 佐剂或无佐剂的动物以及接受免疫佐剂的动物中，任何时候都未检测到针对 OSP 或 LPS 的 IgG 抗体反应。在接受佐剂免疫后，反应最高。接受 OSP:TThc 佐剂或无佐剂的小鼠以及接受未结合 OSP 的小鼠均检测到血清抗 OSP IgM 反应。血清抗 LPS IgM 和弧菌杀菌反应在所有疫苗组中均有检测到，除了接受单独免疫佐剂的小鼠。在任何一组中均未检测到显著的 IgA 抗 OSP 或抗 LPS 反应。给予 OSP:TThc 和佐剂还诱导了针对 OSP 的记忆 B 细胞反应，并在小鼠致死性霍乱攻毒模型中实现了 95%的保护效力。
我们在小鼠中描述了一种具有保护免疫原性的霍乱结合物。霍乱结合疫苗的开发可能有助于诱导长期保护性免疫，特别是在对多糖抗原反应不佳的幼儿中。
