Vaxart, Inc., South San Francisco, California, USA.
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
J Infect Dis. 2020 Mar 2;221(6):919-926. doi: 10.1093/infdis/jiz540.
Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM).
A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses.
Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells.
GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates.
人类诺如病毒（HuNoV）是导致肠胃炎的主要原因。目前尚无预防诺如病毒病或感染的疫苗。需要安全、有感染力的挑战株来评估疫苗在人体感染控制模型（CHIM）中的功效。
制备了诺如病毒株诺瓦克病毒（[NV] GI.1）的储备。健康、遗传易感的成年人接种 NV 001-09NV 号，并监测感染、肠胃炎症状和免疫反应。
001-09NV 号在 16 名遗传易感的个体中引起了 9 例（56%）肠胃炎和 11 例（69%）感染。所有感染的个体均对 GI.1 产生强烈的免疫反应，与基线相比，阻断滴度（BT50）增加了 30 倍（几何平均滴度），GI.1 特异性 IgG 滴度增加了 161 倍。感染后 9 天，外周血中观察到 GI.1 特异性细胞反应，平均每百万外周血单核细胞中有 3253 个 IgA 和 1227 个 IgG 抗体分泌细胞。
GI.1 001-09NV 号似乎与 NV 8fIIa 株的先前传代在毒力上相似。安全性、攻击率和疾病持续时间使 GI.1 001-09NV 号成为未来旨在建立免疫相关性的疫苗研究的有用挑战株。
