Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.
Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.
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DOI：
10.1038/mtm.2015.18
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发表时间：
2015
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影响因子：
--
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中科院分区：
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呼吸道合胞病毒(RSV)是导致婴幼儿和老年人严重呼吸道疾病的主要原因。目前没有疫苗可用于满足这一未得到满足的主要医疗需求。为了诱导中和抗体和广泛的细胞免疫，我们研制了一种基于黑猩猩腺病毒(PanAd3-RSV)和编码RSV F、N和M2-1蛋白的改良痘苗病毒(MVA-RSV)的新的基因疫苗。由于RSV感染仅限于呼吸道，我们比较了鼻内(IN)和肌肉(M)给药在不同物种中的安全性、免疫原性和有效性。单独接种IN或IM疫苗可完全保护BALB/c小鼠和棉花大鼠免受呼吸道合胞病毒在肺部的复制。然而，只有注射IN才能预防上呼吸道感染。肌注MVA-RSV疫苗还可以在没有可检测到的中和抗体的情况下保护棉鼠免受下呼吸道感染。PanAd3-RSV和MVA-RSV的异种加强免疫可在非人灵长类动物中诱导高中和抗体效价和广泛的T细胞反应。此外，鼻腔注射的动物产生了针对F蛋白的粘膜免疫球蛋白A。总之，我们已经证明我们的载体RSV疫苗在灵长类动物模型中诱导了强大的细胞和体液反应，为临床测试提供了强有力的支持。
Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.
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影响因子：
12.4
作者：
Capone, Stefania;Naddeo, Mariarosaria;Folgori, Antonella
通讯作者：
Folgori, Antonella
影响因子：
158.5
作者：
HALL, CB;POWELL, KR;COHEN, HJ
通讯作者：
COHEN, HJ
影响因子：
5.4
作者：
Hussell, T;Baldwin, CJ;Openshaw, PJM
通讯作者：
Openshaw, PJM
DOI：
10.1089/jam.1999.12.275
发表时间：
1999-12-01
期刊：
JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
影响因子：
--
作者：
Brand, P;H채ussinger, K;Heyder, J
通讯作者：
Heyder, J
影响因子：
5.4
作者：
Kim, Eun;Okada, Kaori;Gambotto, Andrea
通讯作者：
Gambotto, Andrea