Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial.
Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial.
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DOI：
10.1093/infdis/jix572
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发表时间：
2018-01-30
期刊：
影响因子：
--
通讯作者：
Van Damme P
中科院分区：
文献类型：
--
作者：
Leroux-Roels G;Cramer JP;Mendelman PM;Sherwood J;Clemens R;Aerssens A;De Coster I;Borkowski A;Baehner F;Van Damme P
二价（GI. 1和GII. 4）病毒样颗粒诺如病毒候选疫苗制剂耐受性良好且具有免疫原性，1剂诱导的免疫应答持续长达1年，包含单磷酰脂质A或给予第二剂不会增加免疫应答。我们研究了1-2剂不同的二价病毒样颗粒（VLP）诺如病毒候选疫苗（NoV）制剂在18- 64岁健康人群中的安全性和免疫原性。在第1天和第28天，参与者（n = 420）随机分为14个相等的组，接受肌内对照疫苗（甲型肝炎）或11种NoV制剂中的1种，这些制剂含有不同剂量的GI. 1和GII. 4c基因型VLP抗原与氢氧化铝[Al（OH）3]，以及0 μg、15 μg或50 μg单磷酰脂质A（MPL）。在第1、28、56、208和393天评估免疫原性。记录征集性局部和全身反应7天，非征集性不良事件（AE）至第56天，以及整个试验期间的严重AE。到第56天，所有NoV制剂诱导泛免疫球蛋白、免疫球蛋白A和组织血型结合抗原阻断抗体的相似增加，主要是在1次给药后，其持续高于基线至第393天。较高的GI.1含量干扰了GII.4c反应，并且反应没有从MPL中受益。总体反应原性主要包括轻度注射部位疼痛、头痛和疲乏。未报告疫苗相关严重AE。所有候选NoV制剂均耐受良好。总体而言，15 μg GI.1/50 μg GII.4c引起免疫原性的最佳平衡，MPL无明显获益，是临床开发中正在推进的候选制剂。NCT 02038907。
Bivalent (GI.1 and GII.4) virus-like particle norovirus candidate vaccine formulations were well tolerated and immunogenic, 1 dose inducing immune responses that persisted up to 1 year, which were not increased by inclusion of monophosphoryl lipid A or administration of a second dose. We investigated safety and immunogenicity of 1–2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18- to 64-year-olds. On days 1 and 28, participants (n = 420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or 1 of 11 NoV formulations containing varying dosages of GI.1 and GII.4c genotype VLP antigens with aluminum hydroxide [Al(OH)3], and 0 μg, 15 μg, or 50 μg monophosphoryl lipid A (MPL). Immunogenicity was assessed on days 1, 28, 56, 208 and 393. Solicited local and systemic reactions were recorded for 7 days, unsolicited adverse events (AEs) until day 56, and serious AEs throughout the trial. All NoV formulations induced similar increases in pan-immunoglobulin, immunoglobulin A, and histo-blood group binding antigen-blocking antibodies by day 56, mostly after 1 dose, that persisted above baseline to day 393. Higher GI.1 content interfered with GII.4c responses, and responses did not benefit from MPL. Overall reactogenicity consisted of mainly mild injection site pain, headache, and fatigue. No vaccine-related serious AEs were reported. All candidate NoV formulations were well tolerated. Overall, 15 μg GI.1/50 μg GII.4c elicited the best balance of immunogenicity with no clear benefit of MPL, and is the candidate formulation being taken forward in clinical development. NCT02038907.
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DOI：
10.1056/nejmoa1101245
发表时间：
2011-12-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Atmar RL;Bernstein DI;Harro CD;Al-Ibrahim MS;Chen WH;Ferreira J;Estes MK;Graham DY;Opekun AR;Richardson C;Mendelman PM
通讯作者：
Mendelman PM
影响因子：
4.6
作者：
Beran, Jiri
通讯作者：
Beran, Jiri
影响因子：
6.4
作者：
Treanor, John J.;Atmar, Robert L.;Mendelman, Paul M.
通讯作者：
Mendelman, Paul M.
影响因子：
4.6
作者：
Szarewski, Anne
通讯作者：
Szarewski, Anne
DOI：
10.1093/infdis/jiu497
发表时间：
2015-03-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Bernstein DI;Atmar RL;Lyon GM;Treanor JJ;Chen WH;Jiang X;Vinjé J;Gregoricus N;Frenck RW Jr;Moe CL;Al-Ibrahim MS;Barrett J;Ferreira J;Estes MK;Graham DY;Goodwin R;Borkowski A;Clemens R;Mendelman PM
通讯作者：
Mendelman PM