A porcine adenovirus with low human seroprevalence is a promising alternative vaccine vector to human adenovirus 5 in an H5N1 virus disease model.

A porcine adenovirus with low human seroprevalence is a promising alternative vaccine vector to human adenovirus 5 in an H5N1 virus disease model.
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在H5N1病毒疾病模型中,具有人类血清阳性率低的猪腺病毒是人类腺病毒5的有前途的替代疫苗。

DOI:
10.1371/journal.pone.0015301
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发表时间:
2010-12-16
期刊:
影响因子:
3.7
通讯作者:
Kobinger G
Kobinger G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Patel A;Tikoo S;Kobinger G

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人腺病毒5型(AdHu5)载体是强大的疫苗平台,然而,自然获得的中和抗体的存在可能会降低载体的有效性和重新给药的潜力。这项研究使用禽流感H5N1疾病模型评估了复制不能的猪腺病毒3型(PAV3)载体作为AdHu5的替代疫苗接种后的免疫反应和保护。用表达优化的A/Hanoi/30408/2005H5N1血凝素抗原(PAV3-HA)的不同剂量的PAV3载体免疫BALB/c小鼠,并与AdHu5-HA对照进行比较。与AdHu5-HA相比,PAV3-HA迅速产生抗体反应,第21天有显著的中和抗体滴度,第8天检测到更强的细胞免疫反应。在攻击前8天接种的PAV3-HA疫苗显示出更高的存活率和更低的病毒载量。在接种后12个月的长期疫苗效果评估表明,PAV3-HA疫苗比AdHu5-HA疫苗具有更好的保护作用。重要的是,与AdHu5相反,PAV3载体不会被来自10,000多个个体的人类抗体显著中和。总体而言,基于PAV3的载体能够介导快速、强大的免疫反应,并提供了一种有前景的AdHu5替代品。
Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5.
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