Mice with diverse microbial exposure histories as a model for preclinical vaccine testing.
Mice with diverse microbial exposure histories as a model for preclinical vaccine testing.
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DOI：
10.1016/j.chom.2021.10.001
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发表时间：
2021-12-08
影响因子：
30.3
通讯作者：
Langlois RA
中科院分区：
文献类型：
--
作者：
Fiege JK;Block KE;Pierson MJ;Nanda H;Shepherd FK;Mickelson CK;Stolley JM;Matchett WE;Wijeyesinghe S;Meyerholz DK;Vezys V;Shen SS;Hamilton SE;Masopust D;Langlois RA
实验室小鼠是临床前疫苗试验的快速模型；然而，这些模型中的疫苗免疫原性往往不能充分转化为人类。重建特定无病原体（SPF）小鼠的生理微生物体验可诱导持久的免疫变化，更好地概括人类免疫。我们研究了不同微生物的小鼠在接种疫苗后是否能更好地模拟人类的反应。我们将实验室小鼠与宠物店小鼠放在一起，它们有不同的微生物暴露，然后评估对流感疫苗的免疫反应。人类对流感疫苗的转录反应在冷藏小鼠中得到了更好的概括。尽管SPF小鼠和封闭小鼠对急性流感感染相当敏感，但封闭小鼠的疫苗诱导的体液反应被抑制，导致对攻击的控制较差。此外，保护性异亚型T细胞免疫在冷藏小鼠中受到损害。由于SPF小鼠在流感疫苗接种时夸大了体液和T细胞的保护作用，因此通过共住重建实验室小鼠的微生物体验可能更好地为临床前疫苗试验提供信息。研究动物被安置在干净的设施中，以减少微生物暴露带来的混杂变量。Fiege等人证明，小鼠的自然微生物暴露导致疫苗接种后的特征与人类更相似。此外，它们还表明，在清洁设施中的动物对流感疫苗的免疫原性会夸大。
Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post-vaccination. We cohoused laboratory mice with pet store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in cohoused mice. Although SPF and cohoused mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in cohoused mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic T cell immunity was compromised in cohoused mice. Because SPF mice exaggerated humoral and T cell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through cohousing may better inform preclinical vaccine testing. Research animals are housed in clean facilities to reduce confounding variables from microbial exposure. Fiege et al demonstrate that natural microbial exposure of mice results in signatures post-vaccination that are more similar to humans. Additionally, they demonstrate that animals in clean facilities exaggerate the immunogenicity to influenza vaccination.
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DOI：
10.1073/pnas.1522376113
发表时间：
2016-04-05
影响因子：
11.1
作者：
Hamilton, Jennifer R.;Sachs, David;Heaton, Nicholas S.
通讯作者：
Heaton, Nicholas S.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
7.8
作者：
Clemens EB;van de Sandt C;Wong SS;Wakim LM;Valkenburg SA
通讯作者：
Valkenburg SA
影响因子：
--
作者：
Chioato, A.;Noseda, E.;Kleinschmidt, A.
通讯作者：
Kleinschmidt, A.
影响因子：
7.7
作者：
Franco LM;Bucasas KL;Wells JM;Niño D;Wang X;Zapata GE;Arden N;Renwick A;Yu P;Quarles JM;Bray MS;Couch RB;Belmont JW;Shaw CA
通讯作者：
Shaw CA