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Assessment of the Duration of Protection in Campylobacter jejuni Experimental Infection in Humans

机译：空肠弯曲杆菌实验性感染的保护期评估。

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A human Campylobacter jejuni infection model provided controlled exposure to assess vaccine efficacy and investigate protective immunity for this important diarrheal pathogen. A well-characterized outbreak strain, C. jejuni 81-176, was investigated using a volunteer experimental infection model to evaluate the dose range and duration of protection. Healthy Campylobacter-seronegative adults received C. jejuni strain 81-176 via oral inoculation of 105, 107, or 109 CFU (5 adults/dose), which was followed by clinical and immunological monitoring. Based on dose range clinical outcomes, the 109-CFU dose (n = 31) was used to assess homologous protection at 28 to 49 days (short-term veterans [STV]; n = 8) or 1 year (long-term veterans [LTV]; n = 7) after primary infection. An illness dose effect was observed for na?ve subjects (with lower doses, 40 to 60% of the subjects were ill; with the 109-CFU dose, 92% of the subjects were ill) along with complete protection for the STV group and attenuated illness for the LTV group (57%). Partial resistance to colonization was seen in STV (25% of the subjects were not infected; 3-log-lower maximum excretion level). Systemic and mucosal immune responses were robust in na?ve subjects irrespective of the dose or the severity of illness. In contrast, in STV there was a lack of circulating antibody-secreting cells (ASC), reflecting the local mucosal effector responses. LTV exhibited comparable ASC responses to primary infection, and anamnestic fecal IgA responses likely contributed to self-resolving illness prior to antibiotic treatment. Campylobacter antigen-dependent production of gamma interferon by peripheral blood mononuclear cells was strongly associated with protection from illness, supporting the hypothesis that TH1 polarization has a primary role in acquired immunity to C. jejuni. This study revealed a C. jejuni dose-related increase in campylobacteriosis rates, evidence of complete short-term protection that waned with time, and immune response patterns associated with protection.
机译：空肠弯曲杆菌人感染模型提供了可控制的暴露水平，以评估疫苗效力并研究这种重要的腹泻病原体的保护性免疫。一个特征明确的爆发株， C。使用自愿性实验感染模型对空肠81-176进行了研究，以评估保护的剂量范围和持续时间。健康的<弯曲>弯曲杆菌血清阴性的成年人接受了 C。空腹接种10 5 ，10 7 或10 9 CFU的空肠菌株81-176（5位成人/剂量） ，然后进行临床和免疫学监测。根据剂量范围的临床结果，使用10 9 -CFU剂量（ n = 31）评估28至49天（短期退伍军人[STV] ]; n = 8）或原发感染后1年（长期退伍军人[LTV]; n = 7）。观察到初次受试者的疾病剂量效应（较低剂量时，有40％至60％的受试者患病;使用10 9 -CFU剂量时，有92％受试者患病）对STV组具有完全的保护，对LTV组具有减轻的疾病（57％）。在STV中观察到对定植的部分抗性（25％的受试者未感染;最大排泄水平降低了3个对数）。初次受试者的全身和粘膜免疫反应均很强，无论其剂量或疾病的严重程度如何。相反，在STV中，缺乏循环的抗体分泌细胞（ASC），反映了局部的粘膜效应子反应。 LTV对原发感染表现出可比的ASC反应，而粪便IgA记忆消除反应可能在抗生素治疗之前导致了自我解决的疾病。外周血单核细胞弯曲杆菌抗原依赖性γ干扰素的产生与疾病防护密切相关，支持了TH1极化在获得对 C的免疫中起主要作用的假说。空肠。这项研究显示了 C。空肠弯曲菌病发病率的剂量相关性增加，随着时间的流逝完全的短期保护的证据以及与保护有关的免疫反应模式。

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