A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector

Junpei Ohtsuka,Akira Mizoguchi,Masayuki Fukumura,Masato Tsurudome,Kenichiro Hara,Aika Kaito,Ayato Takada,Nobuyuki Tsuda,Hiroko Miyamoto,Shujie Wang,Tetsuya Nosaka,Mitsuyo Maeda,Yosky Kataoka,Wakako Furuyama

doi:10.1038/s41598-019-49579-y

Abstract

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.

Highlights

Life-threatening viruses such as Ebola virus (EBOV), SARS coronavirus, and avian influenza virus, emerge unexpectedly
The resultant vaccine BC-PIV/EBOV-GP incorporated a large amount of GP protein on the viral particles, as shown in the Western blot analysis (Fig. 1c)
It is noteworthy that mice are not permissive for human parainfluenza virus type 2 (hPIV2) transcription and replication[20]

Summary

Introduction

Life-threatening viruses such as Ebola virus (EBOV), SARS coronavirus, and avian influenza virus, emerge unexpectedly. A reverse genetics method to generate clonal populations of recombinant RNA viruses enabled us to use hPIV2 as a vector for efficient transgene expression[1,2,3]. BC-PIV is able to induce gene expression nearly 100 times more efficiently than a conventional retroviral vector in human dendritic cells[3]. We report that does BC-PIV vector highly express ectopic antigen in infected cells[3,5], but it displays a large amount of ectopic antigen on the viral envelope, enabling it to skip the translation process in host cells, similar to virus-like particles (VLPs). Across the viral envelope and proper steric structure of the exogenous protein expressed on the envelope to induce neutralization antibodies against it, by using the replication-defective and highly efficient vector, BC-PIV

Methods

Results

Conclusion