Abstract:
The influenza vaccines currently approved for clinical use mainly include inactivated influenza virus vaccines and live attenuated influenza vaccines (LAIVs). LAIVs have multiple advantages, such as ease of use and strong immunogenicity, and can provide cross-protection. In this study, the M gene of the PR8 virus was mutated as follows (G11T, C79G, G82C, C85G, and C1016A), and a live attenuated influenza virus containing the mutated M gene was rescued and obtained using reverse genetic technology as a vaccine candidate. The replication ability of the rescued virus was significantly weakened in both MDCK cells and mice with attenuated virulence. Studies on immunogenicity found that 1000 TCID50 of mutated PR8 (mPR8) can prime strong humoral and cellular immune responses. Single-dose immunization of 1000 TCID50 mPR8 was not only able to counter the challenge of the homologous PR8 virus but also provided cross-protection against the heterologous H9N2 virus.
摘要:
目前批准临床使用的流感疫苗主要包括流感病毒灭活疫苗和流感减毒活疫苗(LAIV)。LAIV有多重优势,如易用性和强免疫原性,可以提供交叉保护。在这项研究中,PR8病毒的M基因突变如下(G11T,C79G,G82C,C85G,andC1016A),用反向基因技术解救并获得含有突变M基因的减毒流感病毒作为疫苗候选物。在MDCK细胞和毒力减弱的小鼠中,被拯救病毒的复制能力均显着减弱。对免疫原性的研究发现,1000TCID50的突变型PR8(mPR8)可以引发强烈的体液和细胞免疫应答。1000TCID50mPR8的单剂量免疫不仅能够对抗同源PR8病毒的攻击,而且还提供针对异源H9N2病毒的交叉保护。