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首页> 外文期刊>Vaccine >Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rats
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Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rats

机译：表达呼吸道合胞病毒（RSV）融合蛋白的重组低血清流行腺病毒载体Ad26和Ad35诱导抗棉花RSV感染的保护性免疫

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RSV is an important cause of lower respiratory tract infections in children, the elderly and in those with underlying medical conditions. Although the high disease burden indicates an urgent need for a vaccine against RSV, no licensed RSV vaccine is currently available. We developed an RSV vaccine candidate based on the low-seroprevalent human adenovirus serotypes 26 and 35 (Ad26 and Ad35) encoding the RSV fusion (F) gene. Single immunization of mice with either one of these vectors induced high titers of RSV neutralizing antibodies and high levels of F specific interferon-gamma-producing T cells. A Thl-type immune response was indicated by a high IgG2a/IgG1 ratio of RSV-specific antibodies, strong induction of RSV-specific interferon-gamma and tumor necrosis factor-alpha cytokine producing CD8 Tcells, and low RSV-specific CD4 T-cell induction. Both humoral and cellular responses were increased upon a boost with RSV-F expressing heterologous adenovirus vector (Ad35 boost after Ad26 prime or vice versa). Both single immunization and prime-boost immunization of cotton rats induced high and long-lasting RSV neutralizing antibody titers and protective immunity against lung and nasal RSV A2 virus load up to at least 30 weeks after immunization. Cotton rats were also completely protected against challenge with a RSV B strain (B15/97) after heterologous prime-boost immunization. Lungs from vaccinated animals showed minimal damage or inflammatory infiltrates post-challenge, in contrast to animals vaccinated with formalin-inactivated virus. Our results suggest that recombinant human adenoviral Ad26 and Ad35 vectors encoding the RSV F gene have the potential to provide broad and durable protection against RSV in humans, and appear safe to be investigated in infants. (C) 2015 The Authors. Published by Elsevier Ltd.
机译：RSV是导致儿童，老年人和患有基础疾病的人下呼吸道感染的重要原因。尽管疾病负担高表明迫切需要针对RSV的疫苗，但目前尚无获得许可的RSV疫苗。我们基于编码RSV融合（F）基因的低血清型人腺病毒血清型26和35（Ad26和Ad35）开发了一种RSV疫苗候选物。用这些载体中的任一种对小鼠进行单次免疫诱导了高滴度的RSV中和抗体和高水平的产生F特异性干扰素-γ的T细胞。 RShl特异性抗体的IgG2a / IgG1比率高，RSV特异性干扰素-γ和肿瘤坏死因子-α细胞因子产生的CD8 T细胞的强烈诱导和RSV特异性CD4 T细胞的低诱导表明Thl型免疫应答感应。用表达RSV-F的异源腺病毒载体加强免疫后，体液和细胞应答均增加（Ad26初次免疫后Ad35加强免疫，反之亦然）。棉鼠的单次免疫和初免-加强免疫均可诱导高和持久的RSV中和抗体滴度，并在免疫后至少30周内抵抗针对肺和鼻RSV A2病毒的保护性免疫。异源初免-加强免疫后，棉鼠也完全受到RSV B株（B15 / 97）的攻击保护。与接种了福尔马林灭活病毒的动物相比，接种疫苗的动物的肺部攻击后的损害或炎症浸润最小。我们的结果表明，编码RSV F基因的重组人腺病毒Ad26和Ad35载体具有提供针对人类RSV的广泛而持久的保护的潜力，并且似乎可以在婴儿中进行安全研究。 （C）2015作者。由Elsevier Ltd.发布

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