Landrum Michael L, Lalani Tahaniyat, Niknian Minoo, Maguire Jason D, Hospenthal Duane R, Fattom Ali, Taylor Kimberly, Fraser Jamie, Wilkins Kenneth, Ellis Michael W, Kessler Paul D, Fahim Rafaat E F, Tribble David R
a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.
b Division of Infectious Diseases , San Antonio Military Medical Center , Fort Sam Houston , TX , USA.
Hum Vaccin Immunother. 2017 Apr 3;13(4):791-801. doi: 10.1080/21645515.2016.1248326. Epub 2016 Dec 23.
We conducted a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults to evaluate the safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens, recombinant α-toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV). 176 subjects were enrolled and randomized within 1 of 11 treatment cohorts: monovalent rAT or rLukS-PV dosages of 10, 25, 50, and 100 μg; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 μg; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 μg bivalent cohort received a second injection on Day 84 and were assessed on Days 98 and 112. Incidence and severity of reactogenicity and adverse events (AEs) were compared. Geometric mean serum concentrations (GMC) and neutralizing activity of anti-rAT and anti-rLukS-PV IgG were assessed. Reactogenicity incidence was significantly higher in vaccine than placebo recipients (77% versus 55%, respectively; p = 0.006). However, 77% of reactogenicity events were mild and 19% were moderate in severity. The AE incidence and severity were similar between the cohorts. All monovalent and bivalent rAT dosages resulted in a significant increase in the anti-rAT IgG and anti- rLukS-PV GMCs between day 0 and 28 compared with placebo, and persisted through Day 84. Exploratory subgroup analyses suggested a higher GMC and neutralizing antibody titers for the 50 μg monovalent or bivalent rAT and rLukS-PV dose as compared to the other doses. No booster effect was observed after administration of the second dose. We conclude that the rAT and rLukS-PV vaccine formulations were well-tolerated and had a favorable immunogenicity profile, producing antibody with neutralizing activity through day 84. There was no benefit observed with a booster dose of the vaccine.
我们在健康成年人中开展了一项随机、双盲、安慰剂对照的剂量递增研究，以评估重组金黄色葡萄球菌候选疫苗抗原、重组α - 类毒素（rAT）和杀白细胞素Panton - Valentine亚单位（rLukS - PV）的安全性和免疫原性。176名受试者被纳入研究，并随机分配至11个治疗组中的1组：单价rAT或rLukS - PV剂量分别为10、25、50和100μg；二价rAT:rLukS剂量分别为10:10、25:25和50:50μg；以及明矾或生理盐水安慰剂。所有受试者在第0、7、14、28和84天进行评估。50:50μg二价组的受试者在第84天接受第二次注射，并在第98和112天进行评估。比较了反应原性和不良事件（AE）的发生率及严重程度。评估了抗rAT和抗rLukS - PV IgG的几何平均血清浓度（GMC）和中和活性。疫苗接种者的反应原性发生率显著高于安慰剂接受者（分别为77%和55%；p = 0.006）。然而，77%的反应原性事件为轻度，19%为中度。各治疗组之间AE的发生率和严重程度相似。与安慰剂相比，所有单价和二价rAT剂量在第0天至28天均导致抗rAT IgG和抗rLukS - PV GMC显著增加，并持续至第84天。探索性亚组分析表明，与其他剂量相比，50μg单价或二价rAT和rLukS - PV剂量的GMC和中和抗体滴度更高。第二次给药后未观察到加强免疫效果。我们得出结论，rAT和rLukS - PV疫苗制剂耐受性良好，具有良好的免疫原性特征，至第84天可产生具有中和活性的抗体。疫苗加强剂量未观察到益处。
