编码呼吸道合胞病毒F蛋白的密码子优化DNA疫苗的免疫原性和效力

Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus.

作者信息

Ternette Nicola, Tippler Bettina, Uberla Klaus, Grunwald Thomas

机构信息

Department of Molecular and Medical Virology, Ruhr-Universitaet Bochum, D-44780 Bochum, Germany.

出版信息

Vaccine. 2007 Oct 10;25(41):7271-9. doi: 10.1016/j.vaccine.2007.07.025. Epub 2007 Aug 23.

DOI:10.1016/j.vaccine.2007.07.025

PMID:17825960

Abstract

Respiratory syncytial virus F-protein (RSV-F) is poorly expressed from DNA expression plasmids containing the wild type RSV-F open reading frame. By codon optimization, premature polyadenylation signals were deleted and a striking enhancement of RSV-F expression levels was achieved. Therefore, the immunogenicity and efficacy of wild type DNA vaccines were compared to codon optimized expression plasmids encoding full-length RSV-F or its ectodomain. Mice were immunized twice with the different DNA vaccines followed by an RSV challenge. Only codon optimized DNA vaccines and in particular the one encoding the ectodomain of RSV-F induced substantial antibody levels and reduced viral load 13-170-fold. Thus, codon optimization enhances the immunogenicity and efficacy of RSV encoding DNA vaccines.

摘要

呼吸道合胞病毒F蛋白（RSV-F）在含有野生型RSV-F开放阅读框的DNA表达质粒中表达不佳。通过密码子优化，删除了过早的聚腺苷酸化信号，并显著提高了RSV-F的表达水平。因此，将野生型DNA疫苗的免疫原性和效力与编码全长RSV-F或其胞外域的密码子优化表达质粒进行了比较。用不同的DNA疫苗对小鼠进行两次免疫，随后进行RSV攻击。只有密码子优化的DNA疫苗，特别是编码RSV-F胞外域的疫苗，诱导了大量抗体水平，并将病毒载量降低了13至170倍。因此，密码子优化增强了编码RSV的DNA疫苗的免疫原性和效力。