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Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis)

机译:减毒痘病毒疫苗载体的感染性和浣熊载体狂犬病疫苗在巴西无尾蝙蝠(Tadarida brasiliensis)中的免疫原性

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Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes. and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 x 10(4) PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats. Published by Elsevier Ltd.
机译:蝙蝠(Chiroptera目)是一类丰富的哺乳动物,具有作为食虫和植物分散剂的巨大生态价值,但在过去的十年中,它们作为人畜共患病疾病的储库而受到了越来越多的关注。为了在自由放养的蝙蝠中控制疾病,我们使用生物光子体内成像和免疫原性研究,对修饰的牛痘安卡拉(MVA)和浣熊痘病毒(RCN)作为巴西无尾蝙蝠(Tadarida brasiliensis)中的潜在疫苗载体进行了测试。 。通过口鼻(ON)或肌内(IM)途径向动物施用表达荧光素酶基因的重组痘病毒载体(MVA-luc,RCN-luc)。然后监测指示病毒感染的生物发光信号。暴露于任何载体后均未发现临床疾病,并且观察到萤光素酶表达受限。用RCN-luc构建体观察到更高和更长的表达水平。当给予IM时,萤光素酶的表达被限制在注射部位,而ON暴露导致在口腔中的初始表达,通常随后在另一个位置的二次复制,可能是胃粘膜或胃相关的淋巴组织。分别在感染后第7天和第9天(dpi)检测到MVA和RCN的口腔拭子中的病毒DNA。虽然在MVA感染的蝙蝠的口腔拭子中未检测到活病毒,但从RCN感染的蝙蝠的口腔拭子中回收的滴度高达3.88 x 10(4)PFU / ml。在用RCN注射IM的两只蝙蝠的粪便样品中也检测到了病毒DNA,但未回收到活病毒。最后,我们检查了ON给药后基于RCN的狂犬病疫苗(RCN-G)的免疫原性。使用快速荧光聚焦抑制试验(RFFIT)在免疫蝙蝠的血清中检测到明显的狂犬病中和抗体滴度。这些研究强调了减毒痘病毒的安全性和免疫原性及其在蝙蝠中作为疫苗载体的潜在用途。由Elsevier Ltd.发布

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