An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes.
An adenovirus prime/plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypes.
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腺病毒素/质粒促进了对两种登革热病毒血清型的均衡免疫反应的促进策略。
DOI：
10.1186/1472-6750-7-10
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发表时间：
2007-02-15
影响因子：
3.5
通讯作者：
Swaminathan, Sathyamangalam
中科院分区：
文献类型：
--
作者：
Khanam, Saima;Rajendra, Pilankatta;Khanna, Navin;Swaminathan, Sathyamangalam
登革热是一个具有全球意义的公共卫生问题，目前既没有有效的抗病毒治疗方法，也没有预防性疫苗。登革热是一种蚊媒病毒性疾病，由黄病毒科成员登革热病毒引起。有四种密切相关的血清型，即DEN-1、DEN-2、DEN-3和DEN-4，每一种血清型都能引起疾病。由于对任何一种血清型的免疫都可能使个体在接触异源血清型时对严重疾病敏感，普遍的共识是有效的疫苗应该是四价的，也就是说，它必须能够提供针对所有四种血清型的保护。目前通过混合四种单价减毒活疫苗病毒来制造四价疫苗制剂的策略揭示了病毒干扰导致倾向于单一血清型的免疫反应表现的现象。这项工作源于以下发现：(1)从疫苗的角度来看，DEN病毒包膜(E)结构域III （EDIII）是分子中最重要的区域；(2)腺病毒（Ad）是一种很有前景的疫苗载体平台。我们描述了一个重组的，复制缺陷的Ad （rAd）载体的构建，该载体编码由框架内连接的DEN病毒血清型2和4的edii组成的嵌合抗原。使用这种rAd载体，与编码相同嵌合二价抗原的质粒载体结合，在初始-增强策略中，我们表明有可能引发针对DEN血清型2和4的等效中和和T细胞反应。我们的数据支持这样的假设，即针对多种血清型的DEN疫苗可以基于单一的基于dna的载体来规避病毒干扰。这项工作为开发一种编码所有四种DEN血清型edii的单一Ad载体奠定了基础，从而引发针对每种DEN血清型的平衡免疫反应。因此，这项工作对开发安全有效的四价登革热疫苗具有重要意义。
Dengue is a public health problem of global significance for which there is neither an effective antiviral therapy nor a preventive vaccine. It is a mosquito-borne viral disease, caused by dengue (DEN) viruses, which are members of the Flaviviridae family. There are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each of which is capable of causing disease. As immunity to any one serotype can potentially sensitize an individual to severe disease during exposure to a heterologous serotype, the general consensus is that an effective vaccine should be tetravalent, that is, it must be capable of affording protection against all four serotypes. The current strategy of creating tetravalent vaccine formulations by mixing together four monovalent live attenuated vaccine viruses has revealed the phenomenon of viral interference leading to the manifestation of immune responses biased towards a single serotype. This work stems from the emergence of (i) the DEN virus envelope (E) domain III (EDIII) as the most important region of the molecule from a vaccine perspective and (ii) the adenovirus (Ad) as a promising vaccine vector platform. We describe the construction of a recombinant, replication-defective Ad (rAd) vector encoding a chimeric antigen made of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this rAd vector, in conjunction with a plasmid vector encoding the same chimeric bivalent antigen, in a prime-boost strategy, we show that it is possible to elicit equipotent neutralizing and T cell responses specific to both DEN serotypes 2 and 4. Our data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has implications for the development of safe and effective tetravalent dengue vaccines.
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影响因子：
1.6
作者：
Jaiswal, S;Khanna, N;Swaminathan, S
通讯作者：
Swaminathan, S
影响因子：
5.5
作者：
Kanesa-thasan, N;Sun, W;Hoke, CH
通讯作者：
Hoke, CH
影响因子：
5.5
作者：
Konishi, E;Kosugi, S;Imoto, JI
通讯作者：
Imoto, JI
DOI：
10.4269/ajtmh.2004.71.811
发表时间：
2004-12-01
影响因子：
3.3
作者：
Blaney, JE;Hanson, CT;Whitehead, SS
通讯作者：
Whitehead, SS
影响因子：
82.9
作者：
Chen, YP;Maguire, T;Marks, RM
通讯作者：
Marks, RM