Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines.
Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines.
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DOI：
10.1371/journal.pone.0005059
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Barry MA
中科院分区：
文献类型：
--
作者：
Weaver EA;Nehete PN;Buchl SS;Senac JS;Palmer D;Ng P;Sastry KJ;Barry MA
所有使用人类血清型 5 腺病毒 (Ad) 载体的研究都必须解决两个主要障碍：安全性和预先存在的中和抗体的存在。辅助依赖性（HD）广告已被提议作为基因治疗和疫苗开发的替代载体，因为它们具有改进的安全性。为了评估 HD-Ad 疫苗的潜力，我们比较了可复制 (RC)、第一代 (FG) 和 HD 载体在小鼠中诱导免疫反应的能力。我们发现 RC-Ad5 和 HD-Ad5 载体比 FG-Ad5 载体产生更强的免疫反应。 HD-Ad5 载体比 RC 或 FG-Ad 具有更低的副作用，产生更低水平的组织损伤和抗 Ad T 细胞反应。此外，HD 载体还具有被所有 C 亚组血清型辅助病毒包装的优点。我们发现 HD 血清型 1、2、5 和 6 同等地诱导抗 HIV 反应。通过异源连续使用这些 HD 血清型，我们表明 HD 载体可用于显着增强小鼠和 FG-Ad5 免疫猕猴的抗 HIV 免疫反应。由于 HD 载体已被证明具有更高的安全性，不具有任何 Ad 基因，可以由多种血清型辅助病毒包装，并引发强烈的抗 HIV 免疫反应，因此它们值得进一步研究，作为 FG 载体的基因疫苗替代品。
All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and anti-Ad T cell responses. Also, HD vectors have the benefit of being packaged by all subgroup C serotype helper viruses. We found that HD serotypes 1, 2, 5, and 6 induce anti-HIV responses equivalently. By using these HD serotypes in heterologous succession we showed that HD vectors can be used to significantly boost anti-HIV immune responses in mice and in FG-Ad5-immune macaques. Since HD vectors have been show to have an increased safety profile, do not possess any Ad genes, can be packaged by multiple serotype helper viruses, and elicit strong anti-HIV immune responses, they warrant further investigation as alternatives to FG vectors as gene-based vaccines.