The right time and place: time- and age-dependent vaccine-enhanced mucosal immunity to parasite infection
The right time and place: time- and age-dependent vaccine-enhanced mucosal immunity to parasite infection
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正确的时间和地点：时间和年龄依赖性疫苗增强对寄生虫感染的粘膜免疫力
DOI：
10.1101/2021.04.28.441781
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Liu W
个体对疫苗接种和随后暴露于感染的反应差异很大，导致感染和传播的持续性。疫苗反应差的普遍存在阻碍了疫苗的开发，特别是针对寄生蠕虫的疫苗。然而，尽管具有重大的经济和社会影响，免疫机制，这种变异性的基础，特别是在寄生虫感染的网站，仍然知之甚少。先前使用原型疫苗控制胃寄生虫Teladorsagia circumcincta（影响绵羊的最高影响寄生虫之一）的试验显示，个体之间的保护作用存在显著差异，我们假设这可能部分是由接种时的年龄驱动的。在这里，为了说明免疫接种羔羊的粘膜感染部位的免疫力是如何发展的，我们在接种前将胃插管插入3个月和6个月大羔羊的真胃中，并在随后的攻击感染期间对其局部免疫反应进行了纵向分析。我们发现，在任何寄生虫暴露发生之前，疫苗引起了皱胃内基线免疫特征的系统性变化，并且一旦羔羊感染，无论年龄如何，都会减少寄生虫负担和卵子产量。然而，年龄影响了接种疫苗的羔羊如何通过多种免疫途径对随后的感染作出反应，只有少数保护性免疫途径与年龄无关。这导致年幼的羔羊更容易感染，无论疫苗状态如何。年龄依赖性（主要是适应性）和年龄无关性（主要是先天性）的保护性免疫途径的鉴定应有助于完善针对这些和潜在的其他反刍动物蠕虫寄生虫的疫苗的配方，并可能更普遍地指示抗蠕虫免疫的特异性。
Individuals vary broadly in their response to vaccination and subsequent exposure to infection, causing persistence of both infection and transmission. The prevalence of poor vaccine responders hampers the development of vaccines, especially against parasitic helminths. Yet despite having substantial economic and societal impact, the immune mechanisms that underlie such variability, especially at the site of parasite infection, remain poorly understood. Previous trials using a prototype vaccine for the control of the gastric parasiticTeladorsagia circumcincta, one of the highest impact parasites affecting sheep, revealed substantial variation in protection between individuals, which we hypothesised may in part be driven by age at vaccination. Here, to characterise how immunity at the mucosal site of infection developed in vaccinated lambs, we inserted gastric cannulae into the abomasa (true stomachs) of three-month- and six-month-old lambs before vaccination, and performed a longitudinal analysis of their local immune response during subsequent challenge infection. We found that the vaccine caused systemic changes in the baseline immune profile within the abomasum before any parasite exposure had occurred and reduced parasite burden and egg output once lambs were infected, regardless of age. However, age affected how vaccinated lambs responded to subsequent infection across multiple immune pathways, with only a minority of protective immune pathways being independent of age. This resulted in younger lambs being more susceptible to infection regardless of vaccine status. The identification of age-dependent (mostly adaptive) and age-independent (mostly innate) protective immune pathways should help refine the formulation of vaccines against these and potentially other helminth parasites of ruminants, and could indicate specificities of anti-helminth immunity more generally.
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影响因子：
4
作者：
Nisbet, Alasdair J.;McNeilly, Tom N.;Matthews, Jacqueline B.
通讯作者：
Matthews, Jacqueline B.
影响因子：
32.4
作者：
Li, Ming O.;Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
5.4
作者：
Faulkner, H;Humphreys, N;Grencis, R
通讯作者：
Grencis, R
影响因子：
9.6
作者：
S. Campbell;S. Nery;J. McCarthy;D. Gray;R. S. Soares Magalhaes;A. Clements
通讯作者：
A. Clements
影响因子：
5.5
作者：
Nisbet, Alasdair J.;McNeilly, Tom N.;Matthews, Jacqueline B.
通讯作者：
Matthews, Jacqueline B.