Subunit Vaccines Using TLR Triagonist Combination Adjuvants Provide Protection Against Coxiella burnetii While Minimizing Reactogenic Responses.
Subunit Vaccines Using TLR Triagonist Combination Adjuvants Provide Protection Against Coxiella burnetii While Minimizing Reactogenic Responses.
复制标题
使用 TLR 三激动剂组合佐剂的亚单位疫苗可提供针对伯内特立克克斯体的保护，同时最大限度地减少反应性反应。
DOI：
10.3389/fimmu.2021.653092
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发表时间：
2021
影响因子：
7.3
通讯作者：
Gregory AE
中科院分区：
文献类型：
--
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
Q热是由专性细胞内细菌贝氏柯克斯体引起的，由于其传播途径、对消毒剂的抗性和低感染剂量，贝氏柯克斯体被指定为生物恐怖主义的潜在病原体。唯一获准用于人类的疫苗是Q-VAX®（Seqirus，在澳大利亚获得许可），这是一种福尔马林灭活的全细胞疫苗，可在先前致敏的个体中产生严重的局部和全身反应原性应答。因此，美国食品和药物管理局和世界各地的其他监管机构一直不愿意批准Q-VAX广泛使用。为了避免这些不良反应，我们制备了含有纯化的CBU 1910、CBU 0307、CBU 0545、CBU 0612、CBU 0891和CBU 1398蛋白和TLR三激动剂佐剂的重组蛋白亚单位疫苗候选物。TLR三激动剂佐剂联合收割机组合不同的TLR激动剂以增强对疫苗抗原的免疫应答。我们在Hartley豚鼠体内用活的C.伯内特氏菌虽然我们所有的候选疫苗在攻毒过程中均表现出不同程度的保护作用，但与福尔马林灭活的全细胞疫苗相比，我们的一种候选疫苗的局部反应原性应答显著降低。我们的研究结果表明，亚单位疫苗与新的TLR三激动剂佐剂结合可以产生针对C.贝氏体感染，同时减少反应原性反应。
Q fever is caused by the obligate intracellular bacterium, Coxiella burnetii, a designated potential agent of bioterrorism because of its route of transmission, resistance to disinfectants, and low infectious dose. The only vaccine licensed for human use is Q-VAX® (Seqirus, licensed in Australia), a formalin-inactivated whole-cell vaccine, which produces severe local and systemic reactogenic responses in previously sensitized individuals. Accordingly, the U.S. Food and Drug Administration and other regulatory bodies around the world, have been reluctant to approve Q-VAX for widespread use. To obviate these adverse reactions, we prepared recombinant protein subunit vaccine candidates containing purified CBU1910, CBU0307, CBU0545, CBU0612, CBU0891, and CBU1398 proteins and TLR triagonist adjuvants. TLR triagonist adjuvants combine different TLR agonists to enhance immune responses to vaccine antigens. We tested both the protective efficacy and reactogenicity of our vaccine candidates in Hartley guinea pigs using intratracheal infection with live C. burnetii. While all of our candidates showed varying degrees of protection during challenge, local reactogenic responses were significantly reduced for one of our vaccine candidates when compared with a formalin-inactivated whole-cell vaccine. Our findings show that subunit vaccines combined with novel TLR triagonist adjuvants can generate protective immunity to C. burnetii infection while reducing reactogenic responses.
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影响因子：
18.2
作者：
Manna S;Howitz WJ;Oldenhuis NJ;Eldredge AC;Shen J;Nihesh FN;Lodoen MB;Guan Z;Esser-Kahn AP
通讯作者：
Esser-Kahn AP
DOI：
10.4049/jimmunol.1302569
发表时间：
2014-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cui W;Joshi NS;Liu Y;Meng H;Kleinstein SH;Kaech SM
通讯作者：
Kaech SM
影响因子：
3.9
作者：
DESSER, RK;EVANS, WH;HIMMELHO.R
通讯作者：
HIMMELHO.R
影响因子：
6
作者：
Lee S;Nguyen MT
通讯作者：
Nguyen MT
影响因子：
7.3
作者：
Chan, Michael;Hayashi, Tomoko;Mathewson, Richard D.;Nour, Afshin;Hayashi, Yuki;Yao, Shiyin;Tawatao, Rommel I.;Crain, Brian;Tsigelny, Igor F.;Kouznetsoya, Valentina L.;Messer, Karen;Pu, Minya;Corr, Maripat;Carson, Dennis A.;Cottamt, Howard B.
通讯作者：
Cottamt, Howard B.