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首页> 外文期刊>Vaccine >Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.
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Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

机译：在SIV感染的非人类灵长类动物中口服鼠伤寒沙门氏菌活疫苗候选物的安全性和耐受性。

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Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques.
机译：非伤寒沙门氏菌（NTS）血清型是全世界急性食源性胃肠炎的常见病因，可导致婴儿，老年人和免疫功能低下的宿主发生侵袭性系统疾病，并伴有高病死率。如在撒哈拉以南非洲那样，在疾病的发生率和死亡率很高且普遍存在多药耐药性的地方，应接种抗侵袭性NTS疾病的疫苗。模拟自然感染的减毒活疫苗是引发保护的一种策略。但是，为了考虑免疫功能低下的受试者，必须特别证明它们已被充分减弱。因此，我们在已建立的慢性猿猴免疫缺陷病毒（SIV）感染的恒河猴猕猴模型中检查了口服减毒鼠伤寒沙门氏菌减毒活疫苗CVD 1921的安全性和耐受性。我们评估了临床参数，组织病理学，并测量了对野生型和疫苗株的粘膜通透性的差异。与感染SIV和未感染SIV的非人类灵长类动物宿主中的野生型鼠伤寒沙门氏菌I77相比，这种减毒活疫苗显示出减少的脱落和全身性扩散，在消化道中表现出有限的病理疾病表现，并且诱导水平低下细胞在组织中的浸润此外，与疫苗株相比，野生型鼠伤寒沙门氏菌诱导肠道上皮损伤和通透性增加，在感染SIV和未感染SIV的非人类灵长类动物中嗜中性粒细胞和巨噬细胞浸润。基于脱落，全身扩散和组织病理学，活减毒鼠伤寒沙门氏菌CVD 1921在非人类灵长类动物模型（包括慢性感染SIV的恒河猴）中似乎是安全且耐受性良好的。

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