Center for Vaccinology (CEVAC), Ghent University and University Hospital, Ghent, Belgium.
Icon Genetics GmbH, a Denka Company, Halle, Germany.
Front Immunol. 2023 Jun 26;14:1188431. doi: 10.3389/fimmu.2023.1188431. eCollection 2023.
The development of an efficacious vaccine against norovirus is of paramount importance given its potential to reduce the global burden of norovirus-associated morbidity and mortality. Here, we report a detailed immunological analysis of a phase I, double-blind, placebo-controlled clinical trial performed on 60 healthy adults, ages 18 to 40. Total serum immunoglobulin and serum IgA against vaccine strains and cross-reactive serum IgG against non-vaccine strains were measured by enzyme immunoassays, whereas cell-mediated immune responses were quantified using intracellular cytokine staining by flow cytometry. A significant increase in humoral and cellular responses, e.g., IgA and CD4 polypositive T cells, was triggered by the GI.4 Chiba 407 (1987) and GII.4 Aomori 2 (2006) VLP-based norovirus vaccine candidate rNV-2v, which is formulated without adjuvant. No booster effect was observed after the second administration in the pre-exposed adult study population. Furthermore, a cross-reactive immune response was elicited, as shown by IgG titers against GI.3 (2002), GII.2 OC08154 (2008), GII.4 (1999), GII.4 Sydney (2012), GII.4 Washington (2018), GII.6 Maryland (2018), and GII.17 Kawasaki 308 (2015). Due to viral infection mucosal gut tissue and the high variety of potentially relevant norovirus strains, a focus should be on IgA and cross-protective humoral and cell-mediated responses in the development of a broadly protective, multi-valent norovirus vaccine.
https://clinicaltrials.gov, identifier NCT05508178. EudraCT number: 2019-003226-25.
鉴于诺如病毒有可能降低全球与诺如病毒相关发病率和死亡率的负担，因此开发一种有效的疫苗至关重要。在此，我们报告了一项对 60 名年龄在 18 至 40 岁之间的健康成年人进行的 I 期、双盲、安慰剂对照临床试验的详细免疫学分析。通过酶联免疫吸附试验测量总血清免疫球蛋白和针对疫苗株的血清 IgA 以及针对非疫苗株的交叉反应性血清 IgG，而通过流式细胞术进行细胞内细胞因子染色来定量细胞介导的免疫反应。GI.4 Chiba 407（1987）和 GII.4 Aomori 2（2006）基于 VLP 的诺如病毒候选疫苗 rNV-2v 引发了体液和细胞反应的显著增加，例如 IgA 和 CD4 阳性 T 细胞，该疫苗候选物无佐剂。在预先暴露的成年研究人群中，第二次给药后没有观察到增强作用。此外，如针对 GI.3（2002）、GII.2 OC08154（2008）、GII.4（1999）、GII.4 Sydney（2012）、GII.4 Washington（2018）、GII.6 Maryland（2018）和 GII.17 Kawasaki 308（2015）的 IgG 滴度所示，引发了交叉反应性免疫反应。由于病毒感染黏膜肠道组织和可能相关的诺如病毒株的多样性，因此应关注 IgA 和交叉保护性体液和细胞介导反应，以开发一种广泛保护、多价的诺如病毒疫苗。
https://clinicaltrials.gov，标识符 NCT05508178。EudraCT 编号：2019-003226-25。
