Enhanced In Vitro Transcytosis of Simian Immunodeficiency Virus Mediated by Vaccine-Induced Antibody Predicts Transmitted/Founder Strain Number After Rectal Challenge
Enhanced In Vitro Transcytosis of Simian Immunodeficiency Virus Mediated by Vaccine-Induced Antibody Predicts Transmitted/Founder Strain Number After Rectal Challenge
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DOI：
10.1093/infdis/jiu300
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发表时间：
2015-01-01
影响因子：
6.4
通讯作者：
Forthal, Donald N.
中科院分区：
文献类型：
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作者：
Gupta, Sandeep;Pegu, Poonam;Forthal, Donald N.
背景。低剂量重复直肠攻击后获得猿猴免疫缺陷病毒 (SIV) 感染的时间与接种 ALVAC-SIV/gp120 或单独 gp120 的猕猴中传播/创始株的数量呈反比。我们确定了疫苗接种后、攻击前血清增强 SIVmac251 跨上皮细胞转胞吞作用的能力是否与传播/创建菌株数相关。方法。通过将血清和 SIVmac251 暴露于 pH 6.0 的人子宫内膜癌 (HEC-1A) 细胞的顶端表面进行转胞吞作用，12 小时后对浸浴基底外侧细胞表面的液体（保持在 pH 7.4）中的病毒进行定量。这些条件允许 Fc 新生儿受体 (FcRn) 依赖性病毒在细胞间穿梭。结果。病毒转胞吞量与传播的变体数量之间存在很强的相关性（R = 0.86，P < .0001）。我们还发现，在反复直肠攻击后仍未感染的 4 只动物的血清转胞吞活性低于随后感染的 19 只动物 (P = .003)。使用免疫组织化学，我们在面对猕猴直肠管腔的柱状上皮细胞上证明了 FcRn。结论。能够通过 FcRn 增强体外转胞吞作用的疫苗诱导抗体可能在确定体内攻击后传播/创始菌株数量和感染结果中发挥作用。
Background. The time to acquisition of simian immunodeficiency virus (SIV) infection following low-dose repeated rectal challenge correlated inversely with the number of transmitted/founder strains among macaques vaccinated with ALVAC-SIV/gp120 or gp120 alone. We determined if the ability of postvaccination, prechallenge sera to enhance SIVmac251 transcytosis across epithelial cells was associated with transmitted/founder strain number.Methods. Transcytosis was carried out by exposing sera and SIVmac251 to the apical surface of human endometrial carcinoma (HEC-1A) cells at pH 6.0 and 12 hours later quantifying virus in fluid bathing the basolateral cell surface (maintained at pH 7.4). These conditions allow Fc neonatal receptor (FcRn)-dependent shuttling of virus across cells.Results. There was a strong correlation between the amount of virus transcytosed and number of transmitted variants (R = 0.86, P < .0001). We also found that 4 animals who remained uninfected after repeated rectal challenges had lower serum transcytosis activity than did 19 animals who subsequently became infected (P = .003). Using immunohistochemistry, we demonstrated FcRn on columnar epithelial cells facing the lumen of the macaque rectum.Conclusions. Vaccine-induced antibody capable of enhancing transcytosis in vitro via FcRn may play a role in determining transmitted/founder strain number and infection outcomes following in vivo challenge.