Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany.
PLoS One. 2013 Aug 14;8(8):e72217. doi: 10.1371/journal.pone.0072217. eCollection 2013.
The Respiratory Syncytial Virus (RSV) and Influenza A Virus (IAV) are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA) of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.
呼吸道合胞病毒(RSV)和甲型流感病毒(IAV)是导致人类严重呼吸道感染的两个主要病原体,每年导致数千人住院和死亡。在这项研究中,我们在小鼠模型中评估了一种组合 DNA 疫苗相对于两种疾病的单价疫苗的免疫原性和疗效。表达 IAV 血凝素(HA)和 RSV F 蛋白的质粒通过肌肉内电穿孔转染,无论单独或联合转染均可诱导强烈的体液免疫反应。因此,检测到高中和抗体滴度,可提供针对 IAV 致死性攻击的保护。此外,接种疫苗的小鼠肺部 RSV 感染后的病毒载量可显著降低。同时,接种疫苗后可测量到大量的抗原特异性、多功能 CD8⁺T 细胞。有趣的是,在存在 RSV-F 编码质粒的情况下,针对血凝素的细胞反应显著降低,但反之则不然。尽管这些结果表明 RSV-F 蛋白具有抑制作用,但组合疫苗的保护效力与单价疫苗相当。总之,针对 RSV 和 IAV 的新型组合疫苗可能具有很大的潜力,在不增加所需疫苗接种次数的情况下降低人类严重呼吸道感染的发生率。