Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus
Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus
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DOI：
10.1128/jvi.01036-09
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发表时间：
2009-12-01
影响因子：
5.4
通讯作者：
Grunwald, Thomas
中科院分区：
文献类型：
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作者：
Kohlmann, Rebekka;Schwannecke, Sarah;Grunwald, Thomas
腺病毒载体(Adv)因其高免疫原性和高效性而在疫苗开发中受到极大关注。以往的研究表明，编码呼吸道合胞病毒(RSV F)融合蛋白密码子优化表达载体的DNA免疫小鼠，与携带RSV F野生型cDNA序列的载体相比，可增强对RSV攻击的保护作用。用AdV-F或AdV-FSOL免疫BALB/c小鼠两次，然后用RSV鼻腔攻击。两种ADV疫苗均能诱导相当水平的RSV F抗体，中和抗体效价最高可达1：900。始终如一地，肺匀浆和支气管肺泡灌洗液中的病毒载量显著减少了6万多倍。即使在加强免疫后8个月，对病毒攻击的保护力也可以测量到。ADV-F和AdV-FSOL诱导的免疫原性和保护效果相似。因此，这些结果鼓励进一步开发针对人类RSV感染的ADV疫苗。
Adenoviral vectors (AdV) have received considerable attention for vaccine development because of their high immunogenicity and efficacy. In previous studies, it was shown that DNA immunization of mice with codon-optimized expression plasmids encoding the fusion protein of respiratory syncytial virus (RSV F) resulted in enhanced protection against RSV challenge compared to immunization with plasmids carrying the wild-type cDNA sequence of RSV F. In this study, we constructed AdV carrying the codon-optimized full-length RSV F gene (AdV-F) or the soluble form of the RSV F gene (AdV-Fsol). BALB/c mice were immunized twice with AdV-F or AdV-Fsol and challenged with RSV intranasally. Substantial levels of antibody to RSV F were induced by both AdV vaccines, with peak neutralizing-antibody titers of 1:900. Consistently, the viral loads in lung homogenates and bronchoalveolar lavage fluids were significantly reduced by a factor of more than 60,000. The protection against viral challenge could be measured even 8 months after the booster immunization. AdV-F and AdV-Fsol induced similar levels of immunogenicity and protective efficacy. Therefore, these results encourage further development of AdV vaccines against RSV infection in humans.