Coxiella burnetii Whole Cell Vaccine Produces a Th1 Delayed-Type Hypersensitivity Response in a Novel Sensitized Mouse Model.
Coxiella burnetii Whole Cell Vaccine Produces a Th1 Delayed-Type Hypersensitivity Response in a Novel Sensitized Mouse Model.
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DOI：
10.3389/fimmu.2021.754712
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发表时间：
2021
影响因子：
7.3
通讯作者：
Samuel JE
中科院分区：
文献类型：
--
作者：
Fratzke AP;Gregory AE;van Schaik EJ;Samuel JE
Q-VAX®是一种全细胞福尔马林灭活疫苗，是唯一获准用于人类预防Q热病原体贝氏柯克斯体的疫苗。虽然这种疫苗提供长期保护，但在先前致敏的个体中，局部和全身反应原性反应很常见，这阻止了其在澳大利亚境外的使用。尽管预防这些不良反应对于开发广泛接受的新型抗C. burnetii，很少有人了解潜在的细胞机制。这主要归因于使用了豚鼠反应原性模型，其中复杂的细胞分析有限。为了解决这个问题，我们比较了三种不同的小鼠品系，建立了C.贝氏全细胞疫苗反应原性应答。SKH 1和C57 Bl/6，而不是BALBc小鼠，在感染或疫苗诱导的致敏后发生局部肉芽肿反应。我们通过使用流式细胞术测量诱导期间疫苗接种部位和脾脏的T细胞群来评估局部和全身应答。与对照组相比，局部反应部位显示致敏小鼠中IFNγ+和IL 17 a + CD 4 T细胞流入，IL 4 + CD 4 T细胞减少。此外，致敏小鼠通过脾脏中IFNγ+和IL 17 a + CD 4 T细胞的增加显示出对激发的全身反应。这些结果表明，局部和系统的C。贝氏反应原性应答与Th 1迟发型超敏反应一致。我们的实验提供了深入了解的病理生理C。C57 B1/6和SKH 1小鼠可作为评价新型贝氏梭菌疫苗反应原性的有价值的模型。贝氏体疫苗候选物。
Q-VAX®, a whole cell, formalin-inactivated vaccine, is the only vaccine licensed for human use to protect against Coxiella burnetii, the cause of Q fever. Although this vaccine provides long-term protection, local and systemic reactogenic responses are common in previously sensitized individuals which prevents its use outside of Australia. Despite the importance of preventing these adverse reactions to develop widely accepted, novel vaccines against C. burnetii, little is understood about the underlying cellular mechanisms. This is mostly attributed to the use of a guinea pig reactogenicity model where complex cellular analysis is limited. To address this, we compared three different mouse strains develop a model of C. burnetii whole cell vaccine reactogenic responses. SKH1 and C57Bl/6, but not BALBc mice, develop local granulomatous reactions after either infection- or vaccine-induced sensitization. We evaluated local and systemic responses by measuring T cell populations from the vaccination site and spleen during elicitation using flow cytometry. Local reaction sites showed influx of IFNγ+ and IL17a+ CD4 T cells in sensitized mice compared with controls and a reduction in IL4+ CD4 T cells. Additionally, sensitized mice showed a systemic response to elicitation by an increase in IFNγ+ and IL17a+ CD4 T cells in the spleen. These results indicate that local and systemic C. burnetii reactogenic responses are consistent with a Th1 delayed-type hypersensitivity. Our experiments provide insights into the pathophysiology of C. burnetii whole cell vaccine reactogenicity and demonstrate that C57Bl/6 and SKH1 mice can provide a valuable model for evaluating the reactogenicity of novel C. burnetii vaccine candidates.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
5.5
作者：
Burny, Wivine;Marchant, Arnaud;Yarzabal, Juan Pablo
通讯作者：
Yarzabal, Juan Pablo
使用TLR三亚贡组合佐剂的亚基疫苗提供了防止Coxiella burnetii的保护，同时最大程度地减少了反应源性反应。
影响因子：
7.3
作者：
Fratzke AP;Jan S;Felgner J;Liang L;Nakajima R;Jasinskas A;Manna S;Nihesh FN;Maiti S;Albin TJ;Esser-Kahn AP;Davies DH;Samuel JE;Felgner PL;Gregory AE
通讯作者：
Gregory AE
影响因子：
82.9
作者：
Gaide O;Emerson RO;Jiang X;Gulati N;Nizza S;Desmarais C;Robins H;Krueger JG;Clark RA;Kupper TS
通讯作者：
Kupper TS
影响因子：
4.8
作者：
Billeskov, Rolf;Beikzadeh, Babak;Berzofsky, Jay A.
通讯作者：
Berzofsky, Jay A.