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改良的新城疫病毒作为一种改进的猴免疫缺陷病毒疫苗载体。

Modified Newcastle Disease virus as an improved vaccine vector against Simian Immunodeficiency virus.

机构信息

Virginia-Maryland College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.

Division of Surgical Sciences, Duke University, Durham, North Carolina, USA.

出版信息

Sci Rep. 2018 Jun 12;8(1):8952. doi: 10.1038/s41598-018-27433-x.

DOI:10.1038/s41598-018-27433-x
PMID:29895833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5997738/
Abstract

SIV infection in macaques is a relevant animal model for HIV pathogenesis and vaccine study in humans. To design a safe and effective vaccine against HIV, we evaluated the suitability of naturally-occurring avirulent Newcastle disease virus (NDV) strains and several modified versions of NDV as vectors for the expression and immunogenicity of SIV envelope protein gp160. All the NDV vectors expressed gp160 protein in infected cells. The gp160 expressed by these vectors formed oligomers and was incorporated into the NDV envelope. All the NDV vectors expressing gp160 were attenuated in chickens. Intranasal immunization of guinea pigs with modified NDV vectors such as rNDV-APMV-2CS/gp160 and rNDV-APMV-8CS/gp160 (NDV strain LaSota containing the cleavage site sequences of F protein of avian paramyxovirus (APMV) serotype 2 and 8, respectively), and rNDV-BC-F-HN/gp160 (NDV strain BC containing LaSota F cleavage site and LaSota F and HN genes) elicited improved SIV-specific humoral and mucosal immune responses compared to other NDV vectors. These modified vectors were also efficient in inducing neutralizing antibody responses to tier 1 A SIVmac251.6 and tier 1B SIVmac251/M766 strains. This study suggests that our novel modified NDV vectors are safe and immunogenic and can be used as vaccine vector to control HIV.

摘要

SIV 感染猕猴是研究 HIV 发病机制和疫苗的相关动物模型。为了设计针对 HIV 的安全有效的疫苗，我们评估了天然弱毒新城疫病毒（NDV）株和 NDV 的几种修饰版本作为 SIV 包膜蛋白 gp160 表达和免疫原性的载体的适用性。所有 NDV 载体均在感染细胞中表达 gp160 蛋白。这些载体表达的 gp160 形成寡聚体并被整合到 NDV 包膜中。所有表达 gp160 的 NDV 载体在鸡中均减毒。用修饰后的 NDV 载体（如 rNDV-APMV-2CS/gp160 和 rNDV-APMV-8CS/gp160（分别含有禽副黏病毒（APMV）血清型 2 和 8 的 F 蛋白裂解位点序列的 LaSota NDV 株）和 rNDV-BC-F-HN/gp160（含有 LaSota F 裂解位点和 LaSota F 和 HN 基因的 BC NDV 株）经鼻腔免疫豚鼠后，与其他 NDV 载体相比，可诱导出更好的 SIV 特异性体液和黏膜免疫应答。这些修饰后的载体也能有效地诱导针对 tier 1A SIVmac251.6 和 tier 1B SIVmac251/M766 株的中和抗体应答。本研究表明，我们新的修饰的 NDV 载体安全且具有免疫原性，可作为控制 HIV 的疫苗载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/52e08aa8abe7/41598_2018_27433_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/5fec3862ee43/41598_2018_27433_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/66a305556f0e/41598_2018_27433_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/ed44464f9dbf/41598_2018_27433_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/d421dc0469c2/41598_2018_27433_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/66b2e2fee442/41598_2018_27433_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/3f5178d32212/41598_2018_27433_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/ebb30356fc3e/41598_2018_27433_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/52e08aa8abe7/41598_2018_27433_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/5fec3862ee43/41598_2018_27433_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/66a305556f0e/41598_2018_27433_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/ed44464f9dbf/41598_2018_27433_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/d421dc0469c2/41598_2018_27433_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/66b2e2fee442/41598_2018_27433_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/3f5178d32212/41598_2018_27433_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/ebb30356fc3e/41598_2018_27433_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb6f/5997738/52e08aa8abe7/41598_2018_27433_Fig8_HTML.jpg

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