以减毒鼠伤寒沙门菌为载体的人呼吸道合胞病毒F蛋白DNA 疫苗滴鼻免疫抗体分析

Antibody responses induced by mucosal DNA vaccine encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium

摘要:

摘要:【目的】以减毒鼠伤寒沙门菌(Salmonella typhimurium aroA strain SL7207，SL7207) 为载体携带可表达呼吸道合胞病毒(Human respiratory syncytial vrius，RSV)密码子优化的融合蛋白(Fusion glycoprotein，F)的真核表达质粒，探讨不同黏膜免疫途径及密码子优化对免疫效果的影响。【方法】通过对RSV 野生型F 基因 (Fwt)进行密码子优化，获得密码子优化的F 基因(Fsyn)，并构建可表达Fsyn 的真核表达质

关键词:关键词: 人呼吸道合胞病毒,F蛋白密码子优化，黏膜免疫，减毒鼠伤寒沙门氏菌SL7207

Abstract:

Abstract:［Objective］ In order to investigate antibody responses by musosal DNA vaccines encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium aroA strain SL7207 (SL7207) via intranasal or intragastric routes．［Methods］After the codon-optimized F gene was synthesized，we constructed eukaryotic expression plasmid pcDNA3.1/Fsyn and transformed it into SL7207 to get recombinant SL7207 of SL7207/pcDNA3.1/Fsyn．Then，SL7207/pcDNA3.1/Fsyn was exploited to evaluate its immunogenicity in BALB/c mice administered intranasally or intragastrically． The resultant serum and mucosal antibody responses were analyzed by indirect ELISA． ［Results］Compared with intragastric immunization group，intranasal immunization group achieved higher level of RSV specific serum IgG and secretion IgA (SIgA)(P＜0.05)．Moreover，F protein expressed by the codon-optimized F gene of Fsyn was of elevated immunogenicity，compared with wild type F (Fwt)(P＜0.05)．［Conclusion］ Intranasal immunization and codon optimization approaches can improve antibody responses of RSV DNA vaccine delivered by attenuated Salmonella typhimurium aroA strain SL7207．

Key words:Keywords: human respiratory syncytial virus，codon-optimized F gene，mucosal administration，attenuated Salmonella typhimurium aroA strain SL7207