A pilot study on use of live attenuated rotavirus vaccine (Rotarix™) as an infection challenge model.
A pilot study on use of live attenuated rotavirus vaccine (Rotarix™) as an infection challenge model.
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使用减毒轮状病毒疫苗 (Rotarix™) 作为感染挑战模型的初步研究。
DOI：
10.1016/j.vaccine.2020.09.023
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发表时间：
2020
期刊：
影响因子：
5.5
通讯作者：
Chilengi R
中科院分区：
文献类型：
--
作者：
Chilengi R
轮状病毒仍然是导致脱水腹泻的最常见原因，特别是在发展中国家。在这些国家的儿童中进行的人类感染挑战研究提供了一个机会，可以快速评估可能提高效力的新候选疫苗。我们评估了Rotarix™作为活减毒攻毒剂的使用情况。方法：我们对22名赞比亚婴儿进行了一项开放标签的探索性研究，这些婴儿在6和10 周龄时接受两种标准剂量的Rotarix™。第一次疫苗剂量被认为是初次疫苗接种，第28天的第二次疫苗剂量被认为是减毒活病毒攻击。在每次给药后的第0、3、5、7、14和28天采集唾液、粪便和血清样本。主要结果为轮状病毒粪便脱落，采用NSP2 qPCR检测。我们计算平均脱落指数为每克粪便病毒拷贝数的自然对数的平均值。第一次注射后，病毒在第3天大量脱落，在第5天达到顶峰。在第二次给药后，大多数婴儿在第3天的病毒脱落量很低，直到第14天才逐渐减少。在所有婴儿和时间点，剂量2后的平均脱落指数显著降低(5.0病毒拷贝/g粪便[95%CI: 0.3-9.7] vs 10.4病毒拷贝/g粪便[95%CI: 6.2-14.6]； p值 < 0.0001;rho = 0.20,SD = 4.97。第28天的血清转化与攻毒剂量后病毒脱落平均减少- 1.03 （95%CI = -8.07,6.01）相关，但这没有统计学意义（p = 0.774）。第28天，唾液和血清中IgA滴度的倍数变化与第0天呈临界正相关；Spearman相关系数，r = 0.69；p = 0.086。与第一次剂量相比，“攻击”剂量后的脱落减少，与第一次剂量诱导粘膜免疫一致。这支持使用Rotarix疫苗作为减毒活疫苗。通过HIC-Vac网络资助医学研究理事会（联合王国）
BackgroundRotavirus remains the commonest cause of dehydrating diarrhoea, particularly in developing countries. Human infection challenge studies in children in these countries offers an opportunity to rapidly evaluate new vaccine candidates that may have improved efficacy. We evaluated use of Rotarix™ as a live-attenuated challenge agent.MethodsWe undertook an open label, exploratory study in infants receiving two standard doses of Rotarix™ at 6 and 10 weeks of age in a cohort of 22 Zambian infants. The first vaccine dose was considered as primary vaccination, and the second at day 28 as a live-attenuated virus challenge. Saliva, stool and serum samples were collected on days 0, 3, 5, 7, 14, and 28 following each dose. The primary outcome was stool shedding of rotavirus, determined by NSP2 qPCR. We calculated mean shedding index as average of natural logarithm of viral copies per gram of stool.FindingsAfter the first dose, viral shedding was high at day 3, peaked by day 5. After the second dose, viral shedding at day 3 was low and reduced gradually in most infants until day 14. Mean shedding index was significantly lower post dose 2 across all infants and timepoints (5.0 virus copies/g of stool [95%CI: 0.3–9.7] vs 10.4 virus copies/g of stool [95%CI: 6.2–14.6]; p-value < 0.0001; rho = 0.20, SD = 4.97. Seroconversion at day 28 was associated with a mean reduction of −1.03 (95%CI = -8.07, 6.01) in viral shedding after challenge dose but this was not statistically significant (p = 0.774). A borderline positive correlation between fold-change in IgA titre at day 28 from day 0 in saliva and serum was observed; Spearman's correlation coefficient, r = 0.69; p = 0.086.InterpretationShedding after the 'challenge' dose was reduced compared with the first dose, consistent with the induction of mucosal immunity by the first dose. This supports the use of Rotarix vaccine as a live-attenuated infection challenge.FundingMedical Research Council (UK) through the HIC-Vac Network
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影响因子：
11.8
作者：
Parashar, Umesh D.;Johnson, Hope;Tate, Jacqueline E.
通讯作者：
Tate, Jacqueline E.
影响因子：
11.8
作者：
Beres, Laura K.;Tate, Jacqueline E.;Chilengi, Roma
通讯作者：
Chilengi, Roma
非洲和亚洲发展中国家婴儿的轮状病毒疫苗：世界卫生组织赞助的咨询的考虑因素。
DOI：
10.1086/605042
发表时间：
2009
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
A. Steele;Manish M Patel;Umesh D. Parashar;J. C. Victor;T. Aguado;K. Neuzil
通讯作者：
K. Neuzil
影响因子：
4.5
作者：
Bosomprah S;Beach LB;Beres LK;Newman J;Kapasa K;Rudd C;Njobvu L;Guffey B;Hubbard S;Foo K;Bolton-Moore C;Stringer J;Chilengi R
通讯作者：
Chilengi R
影响因子：
5.5
作者：
Chan, J.;Nirwati, H.;Danchin, M. D.
通讯作者：
Danchin, M. D.