A Novel Intramuscular Bivalent Norovirus Virus-Like Particle Vaccine Candidate-Reactogenicity, Safety, and Immunogenicity in a Phase 1 Trial in Healthy Adults
A Novel Intramuscular Bivalent Norovirus Virus-Like Particle Vaccine Candidate-Reactogenicity, Safety, and Immunogenicity in a Phase 1 Trial in Healthy Adults
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DOI：
10.1093/infdis/jiu337
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发表时间：
2014-12-01
影响因子：
6.4
通讯作者：
Mendelman, Paul M.
中科院分区：
文献类型：
--
作者：
Treanor, John J.;Atmar, Robert L.;Mendelman, Paul M.
背景诺如病毒是导致胃肠炎相关发病率和死亡率的最重要病毒原因。一项随机、双盲、安慰剂对照研究评估了一种佐剂化的二价肌内诺如病毒样颗粒（VLP）疫苗。48名18 - 49岁的成年人接受了2剂含有基因型GI.1 VLP和共识GII.4 VLP的疫苗或2剂安慰剂。在第一阶段，每种VLP的剂量（5微克、15微克、50微克或150微克）间隔4周给药。随后，年龄为18 - 49岁（n = 16）、50 - 64岁（n = 19）和65 - 85岁（n = 19）的54名成人接受2剂疫苗，每种VLP含50 μ g。在每次给药前和给药后测量总抗体和类特异性抗体应答以及组织相容性抗原组（HBGA）阻断抗体应答。局部反应主要为注射部位疼痛/压痛，未报告发热或疫苗相关严重不良事件。在18 - 49岁、50 - 64岁和65 - 83岁的受试者中，一剂含有50 μ g每种VLP的疫苗分别使GI. 1几何平均滴度（GMT）增加118倍、83倍和24倍，使GI. 4 GMT增加49倍、25倍和9倍。血清抗体应答在第一次给药后第7天达到峰值，第二次给药后没有加强的证据。大多数受试者的HBGA阻断抗体滴度为千分之一日元200。该疫苗具有良好的耐受性和免疫原性。对单次剂量的快速免疫反应可能对军事人员和旅行者以及控制疫情特别有用。
Background. Noroviruses are the most important viral causes of gastroenteritis-related morbidity and mortality. A randomized, double-blind, placebo-controlled study evaluated an adjuvanted bivalent intramuscular norovirus virus-like particle (VLP) vaccine.Methods. Forty-eight adults aged 18-49 years received either 2 doses containing genotype GI.1 VLP and a consensus GII.4 VLP or 2 doses of placebo. Doses (5 A mu g, 15 A mu g, 50 A mu g, or 150 A mu g of each VLP) were administered 4 weeks apart in the first stage. Subsequently, 54 adults, aged 18-49 (n = 16), 50-64 (n = 19), and 65-85 (n = 19) years, received 2 doses of vaccine containing 50 A mu g of each VLP. Total and class-specific antibody responses, as well as histoblood group antigen (HBGA) blocking antibody responses, were measured before and after each dose.Results. Local reactions were mainly injection site pain/tenderness, with no reported fever or vaccine-related serious adverse events. One dose of vaccine containing 50 A mu g of each VLP increased GI.1 geometric mean titers (GMTs) by 118-fold, 83-fold, and 24-fold and increased GII.4 GMTs by 49-fold, 25-fold, and 9-fold in subjects aged 18-49, 50-64, and 65-83 years, respectively. Serum antibody responses peaked at day 7 after the first dose, with no evidence of boosting following a second dose. Most subjects achieved HBGA-blocking antibody titers of a parts per thousand yen200.Conclusions. The vaccine was well tolerated and immunogenic. Rapid immune response to a single dose may be particularly useful in military personnel and travelers and in the control of outbreaks.