Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques

Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques
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DOI:
10.1016/j.vaccine.2006.03.048
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发表时间:
2006-06-05
期刊:
影响因子:
5.5
通讯作者:
Robert-Guroff, Marjorie
Robert-Guroff, Marjorie
中科院分区:
医学3区
文献类型:
--
作者:
Gomez-Roman, V. Raul;Grimes, George J., Jr.;Robert-Guroff, Marjorie

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虽然复制能力腺病毒(Ad)载体在艾滋病疫苗设计中很有前途,但它们在免疫功能低下的宿主中的安全性尚不清楚。为了初步解决这一问题,将含有复制Ad载体的肠溶片口服给感染SHIV和siv的恒河猴,这些恒河猴的CD4 T细胞计数正常、中等或较低且病情稳定。在给药后一周内,在所有动物的粪便中检测到病媒,但在鼻分泌物中未检测到,表明病毒未向上呼吸道传播。在10周的随访期间,所有动物的CD4 T细胞计数和病毒载量保持稳定,未观察到发热、体重减轻或其他ad诱导疾病的临床症状。口服递送复制的Ad载体是安全的,并且对感染SHIV和siv的宿主具有良好的耐受性。在艾滋病毒高流行地区,口服肠溶片可能被证明是安全的,可用于接种可复制的广告载体疫苗。Elsevier Ltd.出版。
Although replication-competent adenovirus (Ad) vectors are promising in AIDS vaccine design, their safety in immune compromised hosts is unknown. To initially address this question, enteric-coated tablets containing a replicating Ad vector were orally administered to SHIV and SIV-infected rhesus macaques with normal, intermediate or low CD4 T cell counts and stable disease. The vector was detected within a week after tablet administration in stools of all animals but not in nasal secretions, indicating no spread of virus to the upper respiratory tract. CD4 T cell counts and viral loads remained stable in all animals and no signs of fever, weight loss, or other clinical symptoms of Ad-induced disease were observed during 10 weeks of follow-up. Oral delivery of the replicating Ad vector was safe and well tolerated by SHIV- and SIV-infected hosts. Oral enteric-coated tablets may prove safe for administering replicating Ad-vectored vaccines in areas with high HIV prevalence. Published by Elsevier Ltd.