人类诺如病毒(HuNoV)是腹泻的主要病毒原因,GII.4是全球HuNoV暴发的主要基因型。然而,新的基因组变种定期出现,使抗HuNoV疫苗的开发复杂化;缺乏其他专门针对HuNoV疾病的预防或治疗药物。使用口服抗HuNoV抗体的被动免疫可能是合理的选择。这里,我们探讨了在人类肠样(HIE)模型中使用鸟类免疫球蛋白(IgY)体外预防HuNoV感染的可行性。
通过肌内注射用GII.4HuNoV毒株(GII.4/CHDC2094/1974/US)的病毒样颗粒(VLP)免疫母鸡。评估所得IgY对组织血型抗原(HBGA)的结合抑制作用以及对代表性GII.4和GII.6临床分离株的病毒中和作用,使用HIE模型。
初次免疫后三周检测到IgY滴度,从9周到23周,持续在1:221(1:2,097,152)的水平。抗HuNoVIgY显著(p<0.05)阻断VLP粘附到HBGA高达1:12,048稀释(0.005mg/mL),并且显着(p<0.05)抑制了HIE高达1:128稀释度(0.08mg/mL)的HuNoVGII.4[P16]Sydney2012的复制。未检测到针对基因型GII.6的中和。
我们通过HuNoVGII.4证明了IgY预防HIE感染的可行性。临床制剂应涵盖多种循环HuNoV基因型以获得综合疗效。动物研究计划正在进行中。
Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model.
Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model.
IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6.
We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.