Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.
Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.
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DOI：
10.1371/journal.pone.0082966
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Saif LJ
中科院分区：
文献类型：
--
作者：
Chattha KS;Kandasamy S;Vlasova AN;Saif LJ
轮状病毒（RV）是儿童胃肠炎的主要原因。广泛的维生素 A 缺乏与发展中国家儿童疫苗功效降低和腹泻感染发病率升高有关。我们建立了维生素 A 缺乏 (VAD) 无菌仔猪模型，模拟儿童亚临床维生素 A 缺乏症，以研究其对口服人轮状病毒 (HRV) 疫苗和强毒 HRV 攻击的影响。来自 VAD 和维生素 A 充足 (VAS) 母猪的仔猪口服减毒 HRV 疫苗或模拟疫苗（添加/不添加补充维生素 A），并用强毒 HRV 进行攻击。与 VAS 对照猪相比，未接种疫苗的 VAD 对照仔猪的肝脏维生素 A 明显较低，腹泻的严重程度和持续时间较高，以及攻击后 HRV 粪便排出。与 VAS 对照猪相比，VAD 中保护作用的降低与血液和肠道组织中先天 (IFNα) 细胞因子和 CD8 T 细胞频率显着升高、促炎 (IL12) 较高和抗炎 (IL10) 细胞因子降低 2-3 倍同时发生。与接种 VAS 的猪相比，接种 VAD 的猪具有更高的腹泻严重程度评分，这与前一组中血清 IgA HRV 抗体滴度较低以及攻击后肠道 IgA 抗体分泌细胞显着降低相一致，表明记忆反应较低。在攻击后，与 VAS 接种组相比，VAD 接种组观察到血清 HRV IgG 抗体较高的趋势。与接种疫苗的 VAS 组相比，接种疫苗的 VAD（未补充维生素 A）猪的血清 IL12 (PID2) 和 IFNγ (PID6) 显着更高，表明 VAD 条件下的 Th1 反应更高。此外，VAD 猪的调节性 T 细胞反应受到损害。在 VAD 猪中补充维生素 A 并不能完全恢复 AttHRV 疫苗失调的免疫反应或中度致命 HRV 腹泻。我们的研究结果表明，发展中国家儿童的 VAD 可能部分导致更严重的轮状病毒感染和 HRV 疫苗功效降低。
Rotaviruses (RV) are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD) gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV) vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS) sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα) cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12) and 2-3 fold lower anti-inflammatory (IL10) cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented) pigs had significantly higher serum IL12 (PID2) and IFNγ (PID6) compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more severe rotavirus infection and lower HRV vaccine efficacy.
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影响因子：
4.5
作者：
Imdad A;Yakoob MY;Sudfeld C;Haider BA;Black RE;Bhutta ZA
通讯作者：
Bhutta ZA
影响因子：
4.3
作者：
Bhaskaram, P.;Rao, K. Visweswara
通讯作者：
Rao, K. Visweswara
影响因子：
3.6
作者：
AHMED, F;JONES, DB;JACKSON, AA
通讯作者：
JACKSON, AA
DOI：
10.4049/jimmunol.1101248
发表时间：
2011-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaufman DR;De Calisto J;Simmons NL;Cruz AN;Villablanca EJ;Mora JR;Barouch DH
通讯作者：
Barouch DH
影响因子：
6.4
作者：
Long, Kurt Z.;Garcia, Coralith;Ko, GwangPyo
通讯作者：
Ko, GwangPyo