A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines.
A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines.
复制标题
DOI：
10.3390/v14122803
复制
发表时间：
2022-12-15
期刊：
影响因子：
--
通讯作者：
Yuan L
中科院分区：
文献类型：
--
作者：
Nyblade C;Hensley C;Parreño V;Zhou P;Frazier M;Frazier A;Ramesh A;Lei S;Degiuseppe JI;Tan M;Yuan L
人轮状病毒（HRV）是5岁以下儿童胃肠炎的主要原因。含有G1 P [8]和G1-4P[8]毒株的许可疫苗对新出现的P[6]毒株的有效性较低，表明迫切需要更好的交叉保护疫苗。在这里，我们报告了我们开发的一种新的P[6] HRV感染和疾病的无菌（Gn）猪模型，作为评估潜在疫苗候选物的工具。Arg HRV（G4 P [6]）毒株来源于腹泻人类婴儿粪便样本，并通过宏基因组测序确定不含其他病毒。用含5.6 × 105个荧光病灶单位（FFU）的粪便悬液经口接种新生Gn猪。在接种后第2或3天收集小肠和大肠内容物。病毒在新生Gn猪中传代6次以产生大的接种物库。接下来，33-34日龄Gn猪经口接种10 - 2、103、104和105 FFU的Arg HRV，以确定最佳攻毒剂量。无论接种剂量如何，所有猪均出现感染的临床体征。最佳攻毒剂量确定为105 FFU。这种新的Gn猪模型可用于评估候选单价和多价疫苗对P[6] HRV的保护效力。
Human rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33–34 day old Gn pigs were orally inoculated with 10−2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.
登录
查看更多内容
影响因子：
9.4
作者：
Bok, K;Palacios, G;Gomez, J
通讯作者：
Gomez, J
影响因子：
4.2
作者：
Lee, Su-Kyung;Choi, Seoheui;Kim, Hyun Soo
通讯作者：
Kim, Hyun Soo
影响因子：
3.8
作者：
Ward, LA;Rosen, BI;Saif, LJ
通讯作者：
Saif, LJ
影响因子：
12.7
作者：
Carmona, RCC;Sampaio, MD;Granato, CFH
通讯作者：
Granato, CFH
影响因子：
3.7
作者：
Steele, Andrew Duncan;Neuzil, Kathleen M.;Han, Htay Htay
通讯作者：
Han, Htay Htay