Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults.
Safety, tolerability, and immunogenicity of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) in healthy Japanese adults.
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DOI：
10.1080/21645515.2018.1496764
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发表时间：
2018
影响因子：
4.8
通讯作者：
Gurtman A
中科院分区：
文献类型：
--
作者：
Inoue M;Yonemura T;Baber J;Shoji Y;Aizawa M;Cooper D;Eiden J;Gruber WC;Jansen KU;Anderson AS;Gurtman A
一种新的金黄色葡萄球菌4抗原疫苗（SA 4Ag）正在开发中，其包含与CRM 197缀合的荚膜多糖血清型5和8（CP 5和CP 8）、重组蛋白凝集因子A（rmClfA）和重组锰转运蛋白C（MntC）。我们在20 - 64岁和65 - 85岁的日本成年人中评价了SA 4Ag的安全性、耐受性和免疫原性。共有136名健康日本成年人（每个年龄组68名）以1：1的比例随机接受单剂量SA 4Ag或安慰剂肌内注射（第1天）。安全性评估包括反应原性和不良事件。疫苗诱导免疫应答的能力被认为是功能性的，因为它们能够促进S.金黄色葡萄球菌或中和S.使用5种不同的抗原特异性测定来评估金黄色葡萄球菌的毒力机制。SA 4Ag在两个年龄组中耐受性良好，没有安全性问题。在第29天，每个年龄组中> 85%的SA 4Ag接受者达到每种抗原的预定阈值。在SA 4Ag组中从基线至第29天的抗体几何平均倍数增加分别为：对于CP 5和CP 8（调理吞噬活性测定），> 80和> 30;对于ClfA（纤维蛋白原结合抑制测定），> 10;以及对于ClfA和MntC（竞争性Luminex®免疫测定），> 15和> 7。抗体滴度下降至第12个月，但仍远高于基线和安慰剂水平。SA 4Ag具有可接受的安全性特征，并在两个年龄组中诱导快速和稳健的功能性免疫应答。这些结果支持正在进行的SA 4Ag预防侵袭性S.金黄色葡萄球菌病的择期手术患者在日本，北美和欧洲。
A novel Staphylococcus aureus 4-antigen vaccine (SA4Ag) is under development, comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant protein clumping factor A (rmClfA), and recombinant manganese transporter protein C (MntC). We evaluated SA4Ag safety, tolerability, and immunogenicity in Japanese adults aged 20 to 64 and 65 to 85 years. A total of 136 healthy Japanese adults (68 per age group) were randomized 1:1 to receive single-dose SA4Ag or placebo intramuscularly (Day 1). Safety assessments included reactogenicity and adverse events. The ability of the vaccine to induce immune responses that are considered functional due to their ability to facilitate the killing of S. aureus or neutralize S. aureus virulence mechanisms was assessed using 5 different antigen-specific assays. SA4Ag was well tolerated in both age groups, with no safety concerns. At Day 29, > 85% of SA4Ag recipients in each age group achieved predefined thresholds for each antigen. Antibody geometric mean-fold rises from baseline to Day 29 in SA4Ag groups were: > 80 and > 30 for CP5 and CP8 (opsonophagocytic activity assay), > 10 for ClfA (fibrinogen-binding inhibition assay), and > 15 and > 7 for ClfA and MntC (competitive Luminex® immunoassay), respectively. Antibody titers decreased through Month 12 but remained well above baseline and placebo levels. SA4Ag had an acceptable safety profile and induced rapid and robust functional immune responses in both age groups. These results support ongoing development of SA4Ag for the prevention of invasive S. aureus disease in elective-surgery patients in Japan, North America, and Europe.
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DOI：
10.1093/infdis/jis272
发表时间：
2012-06
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Anderson AS;Scully IL;Timofeyeva Y;Murphy E;McNeil LK;Mininni T;Nuñez L;Carriere M;Singer C;Dilts DA;Jansen KU
通讯作者：
Jansen KU
影响因子：
--
作者：
Hawkins, Julio;Kodali, Srinivas;Donald, Robert G. K.
通讯作者：
Donald, Robert G. K.
影响因子：
6.4
作者：
Kaye, KS;Schmit, K;Schmader, KE
通讯作者：
Schmader, KE
影响因子：
3.7
作者：
Uematsu H;Yamashita K;Kunisawa S;Fushimi K;Imanaka Y
通讯作者：
Imanaka Y
影响因子：
4.5
作者：
Weiner LM;Webb AK;Limbago B;Dudeck MA;Patel J;Kallen AJ;Edwards JR;Sievert DM
通讯作者：
Sievert DM