Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germfree mice can be colonized and have been used to study OCV immunogenicity. However, germfree animals have impaired immune systems and intestinal physiology; also, live OCVs colonize germfree mice for many months, which does not mimic the clearance kinetics of live OCVs in humans. In this study, we leveraged antibiotic-treated, conventionally raised adult mice to study the effects of transient intestinal colonization by a live OCV V. cholerae strain. In a single-dose vaccination regimen, we found that HaitiV, a live-attenuated OCV candidate, was cleared by streptomycin-treated adult mice within 2 weeks after oral inoculation. This transient colonization elicited far stronger adaptive immune correlates of protection against cholera than did inactivated whole-cell HaitiV. Infant mice from HaitiV-vaccinated dams were also significantly more protected from choleric disease than pups from inactivated-HaitiV-vaccinated dams. Our findings establish the benefits of antibiotic-treated mice for live-OCV studies as well as their limitations and underscore the immunogenicity of HaitiV.

中文翻译：

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减毒的口服霍乱疫苗在肠道中的短暂定植在链霉素治疗的小鼠中引起保护性免疫应答。

当前用于评估口服霍乱活疫苗（OCV）功效的小鼠模型具有重要的局限性。常规饲养的成年小鼠对霍乱弧菌的肠道定殖具有抗性，但是无菌小鼠可以定殖，并已用于研究OCV免疫原性。但是，无菌动物会损害免疫系统和肠道生理。同样，活的OCV在无菌小鼠中定居了许多个月，这不能模仿活的OCV在人体内的清除动力学。在这项研究中，我们利用经抗生素处理的，常规饲养的成年小鼠研究了活的OCV霍乱弧菌对短暂肠菌落的影响。应变。在单剂量疫苗接种方案中，我们发现口服链霉素治疗的成年小鼠清除了活体减毒的OCV候选基因HaitiV。与灭活的全细胞海地病毒相比，这种短暂的定殖引起了更强的针对霍乱的保护性免疫相关性。与来自灭活的HaitiV疫苗的水坝的幼崽相比，来自于HaitiV疫苗的水坝的婴儿小鼠对霍乱病的保护也明显更高。我们的发现确定了用抗生素治疗的小鼠进行实时OCV研究的益处及其局限性，并强调了HaitiV的免疫原性。