Ball J M, Graham D Y, Opekun A R, Gilger M A, Guerrero R A, Estes M K
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas, USA.
Gastroenterology. 1999 Jul;117(1):40-8. doi: 10.1016/s0016-5085(99)70548-2.
BACKGROUND & AIMS: Norwalk virus (NV) is a major cause of epidemic gastroenteritis. The NV capsid is composed of a single protein that forms recombinant (rNV) virus-like particles (VLPs). In mice, these VLPs are immunogenic when administered orally without adjuvant, and they elicit serum immunoglobulin (Ig) G and intestinal IgA responses. The aim of this study was to evaluate the safety and immunogenicity of rNV VLPs in healthy volunteers.
Twenty antibody-positive adults were orally administered rNV VLPs in sterile Milli-Q water on days 1 and 21. Vaccine safety and serum rNV-specific total and subclass IgG and IgA antibody responses were monitored. The immune response induced by the VLPs was compared with the response elicited by replicating virus.
No side effects were observed or reported by the volunteers. Serum IgG responses to rNV VLPs were dose-dependent, and all vaccinees given 250 microgram of rNV VLPs responded with >/=4-fold increases in serum IgG titers. Most of the volunteers (83%; 15 of 18) responded after the first rNV VLP dose and showed no increase in serum IgG titer after the second dose.
Orally administered rNV VLPs are safe and immunogenic in healthy adults when administered without adjuvant and are useful to test the mucosal delivery of immunogens.
诺如病毒（NV）是流行性肠胃炎的主要病因。NV衣壳由单一蛋白质组成，可形成重组（rNV）病毒样颗粒（VLP）。在小鼠中，这些VLP经口服无佐剂给药时具有免疫原性，可引发血清免疫球蛋白（Ig）G和肠道IgA反应。本研究旨在评估rNV VLP在健康志愿者中的安全性和免疫原性。
20名抗体阳性成年人在第1天和第21天口服无菌超纯水配制的rNV VLP。监测疫苗安全性以及血清中rNV特异性总IgG和IgA及亚类IgG和IgA抗体反应。将VLP诱导的免疫反应与复制病毒引发的反应进行比较。
志愿者未观察到或报告有副作用。血清对rNV VLP的IgG反应呈剂量依赖性，所有给予250微克rNV VLP的接种者血清IgG滴度均有≥4倍的升高。大多数志愿者（83%；18名中的15名）在首次给予rNV VLP剂量后有反应，第二次给药后血清IgG滴度未升高。
口服rNV VLP在无佐剂情况下对健康成年人安全且具有免疫原性，有助于测试免疫原的黏膜递送。
