Hyperimmune Targeting Staphylococcal Toxins Effectively Protect Against USA 300 MRSA Infection in Mouse Bacteremia and Pneumonia Models.
Hyperimmune Targeting Staphylococcal Toxins Effectively Protect Against USA 300 MRSA Infection in Mouse Bacteremia and Pneumonia Models.
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DOI：
10.3389/fimmu.2022.893921
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
金黄色葡萄球菌已获得多重耐药性，并已演变成超级细菌，如耐甲氧西林/万古霉素的S。金黄色葡萄球菌（MRSA/VRSA）感染，并且因此是与高发病率和死亡率相关的医院和社区感染的主要原因，对此没有FDA批准的疫苗或生物治疗剂可用。以前针对表面相关抗原的努力在临床测试中失败了。在这里，我们从兔血清中产生了针对六种主要S.金黄色葡萄球菌毒素靶向的实验疫苗（IBT-V02），并证明了显着的效力，抗毒力被动免疫策略。针对来自个体动物血清的六种细胞外毒素分析了广泛的体外结合和中和滴度。所有IBT-V02免疫的动物在第一次加强剂量时引发针对所有成孔疫苗组分的最大免疫应答，而对于疫苗的超抗原（SAg）组分，需要第二次和第三次加强剂量以达到结合和毒素中和滴度的平台。重要的是，由从合并的血清纯化的全长IgG（IBT-V02-IgG）和去物种化的F（ab '）2（IBT-V02-F（ab'）2）组成的两种抗IBT-V02超免疫产物保留了针对IBT-V02靶毒素的结合和中和滴度。F（ab '）2还表现出针对三种白细胞毒素（HlgAB、HlgCB和LukED）和四种SAg（SEC 1、SED、SEK和SEQ）的交叉中和滴度，所述三种白细胞毒素和四种SAg不是IBT-V02的一部分。F（ab '）2还中和了临床上主要的沙门氏菌菌株的细菌培养上清液中的毒素。金黄色。使用USA 300 S在菌血症和肺炎模型中生成的体内疗效数据。金黄色葡萄球菌菌株显示F（ab '）2的剂量依赖性保护。这些有效性数据证实了葡萄球菌毒素是可行的靶点，并支持进一步开发超免疫产品，作为一种潜在的紧急治疗方法，用于治疗危及生命的S。金黄色葡萄球菌感染
Staphylococcus aureus has been acquiring multiple drug resistance and has evolved into superbugs such as Methicillin/Vancomycin-resistant S. aureus (MRSA/VRSA) and, consequently, is a major cause of nosocomial and community infections associated with high morbidity and mortality for which no FDA-approved vaccines or biotherapeutics are available. Previous efforts targeting the surface-associated antigens have failed in clinical testing. Here, we generated hyperimmune products from sera in rabbits against six major S. aureus toxins targeted by an experimental vaccine (IBT-V02) and demonstrated significant efficacy for an anti-virulence passive immunization strategy. Extensive in vitro binding and neutralizing titers were analyzed against six extracellular toxins from individual animal sera. All IBT-V02 immunized animals elicited the maximum immune response upon the first boost dose against all pore-forming vaccine components, while for superantigen (SAgs) components of the vaccine, second and third doses of a boost were needed to reach a plateau in binding and toxin neutralizing titers. Importantly, both anti-staphylococcus hyperimmune products consisting of full-length IgG (IBT-V02-IgG) purified from the pooled sera and de-speciated F(ab’)2 (IBT-V02-F(ab’)2) retained the binding and neutralizing titers against IBT-V02 target toxins. F(ab’)2 also exhibited cross-neutralization titers against three leukotoxins (HlgAB, HlgCB, and LukED) and four SAgs (SEC1, SED, SEK, and SEQ) which were not part of IBT-V02. F(ab’)2 also neutralized toxins in bacterial culture supernatant from major clinical strains of S. aureus. In vivo efficacy data generated in bacteremia and pneumonia models using USA300 S. aureus strain demonstrated dose-dependent protection by F(ab’)2. These efficacy data confirmed the staphylococcal toxins as viable targets and support the further development effort of hyperimmune products as a potential adjunctive therapy for emergency uses against life-threatening S. aureus infections.
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影响因子：
11.8
作者：
Fritz, Stephanie A.;Tiemann, Kristin M.;Hunstad, David A.
通讯作者：
Hunstad, David A.
影响因子：
4.8
作者：
Karauzum, Hatice;Chen, Gang;Aman, M. Javad
通讯作者：
Aman, M. Javad
影响因子：
7.3
作者：
Clegg J;Soldaini E;McLoughlin RM;Rittenhouse S;Bagnoli F;Phogat S
通讯作者：
Phogat S
DOI：
10.1084/jem.20100995
发表时间：
2010-10-25
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Abboud N;Chow SK;Saylor C;Janda A;Ravetch JV;Scharff MD;Casadevall A
通讯作者：
Casadevall A
影响因子：
38.9
作者：
Francois, Bruno;Mercier, Emmanuelle;Laterre, Pierre-Francois
通讯作者：
Laterre, Pierre-Francois