A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector
A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector
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DOI：
10.1038/s41598-019-49579-y
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发表时间：
2019-09-09
影响因子：
4.6
通讯作者：
Nosaka, Tetsuya
中科院分区：
文献类型：
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作者：
Ohtsuka, Junpei;Fukumura, Masayuki;Nosaka, Tetsuya
采用反向遗传学的重组病毒生产方法，将具有适当空间结构的异位蛋白高效地负载到人副流感病毒2型(HPIV2)F基因缺陷的BC-PIV载体的囊膜上。此外，异位抗原肽被成功地负载在载体包膜的外部、内部或两侧。携带埃博拉病毒gP基因的BC-PIV载体能够在小鼠体内诱导中和抗体。此外，带有黑色素瘤gp100和WT1肿瘤抗原抗原表位的BC-PIV在肿瘤移植的同基因小鼠中诱导了CD8+T细胞介导的反应。考虑到亲本hPIV2的低致病性和反复感染，BC-PIV可以作为一种安全性高的通用载体用于重组疫苗的开发，以解决无法满足的医学需求。
Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.