Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic self-adjuvanting glycoconjugate cancer vaccine carriers.
Synthesis and evaluation of monophosphoryl lipid A derivatives as fully synthetic self-adjuvanting glycoconjugate cancer vaccine carriers.
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DOI：
10.1039/c4ob00390j
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发表时间：
2014-05-28
影响因子：
3.2
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Zhou Z;Mondal M;Liao G;Guo Z
全合成糖基肿瘤疫苗是一个极具吸引力的概念，而该领域的一个重要课题是开发合适的疫苗载体，以提高肿瘤相关糖抗原（TACA）的免疫原性和其他免疫学特性。在这种情况下，四个单磷酰衍生物脑膜炎奈瑟氏菌脂质A合成通过一个高度收敛和有效的策略，并评估作为疫苗载体和佐剂。发现这些单磷酰脂质A（MPLA）衍生物与修饰形式的sTn抗原的缀合物在不存在外部佐剂的情况下引发高滴度的抗原特异性IgG抗体，表明T细胞依赖性免疫应答。得出的结论是，MPLA可以用作有效的疫苗载体和内置佐剂，以产生完全合成的自佐剂的基于碳水化合物的癌症疫苗。MPLA的脂质组成和结构对其免疫活性有显著影响，其中天然N。脑膜炎MPLA表现出最有前途的性能。此外，Titermax Gold，一种常规的疫苗佐剂，被发现抑制，而不是促进，MPLA缀合物的免疫活性，可能通过与MPLA相互作用。
Fully synthetic carbohydrate-based cancer vaccine is an attractive concept, while an important topic in the area is to develop proper vaccine carriers that can improve the immunogenicity and other immunological properties of tumor-associated carbohydrate antigens (TACAs). In this context, four monophosphoryl derivatives of Neisseria meningitidis lipid A were synthesized via a highly convergent and effective strategy and evaluated as vaccine carriers and adjuvants. The conjugates of these monophosphoryl lipid A (MPLA) derivatives with a modified form of the sTn antigen were found to elicit high titers of antigen-specific IgG antibodies, indicating T cell-dependent immune response, in the absence of an external adjuvant. It was concluded that MPLA’s could be utilized as potent vaccine carriers and built-in adjuvants to create fully synthetic self-adjuvanting carbohydrate-based cancer vaccines. The lipid composition and structure of MPLA were shown to have a significant influence on its immunological activity, and among the MPLA’s examined, natural N. meningitidis MPLA exhibited the most promising properties. Moreover, Titermax Gold, a conventional vaccine adjuvant, was revealed to inhibit, rather than promote, the immunological activity of MPLA conjugates, maybe via interacting with MPLA text goes here.
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影响因子：
7.8
作者：
Guo, Zhongwu;Wang, Qianli
通讯作者：
Wang, Qianli
DOI：
10.1073/pnas.1115166109
发表时间：
2012-01-03
影响因子：
11.1
作者：
Lakshminarayanan, Vani;Thompson, Pamela;Boons, Geert-Jan
通讯作者：
Boons, Geert-Jan
影响因子：
16.6
作者：
Kaiser, Anton;Gaidzik, Nikola;Kunz, Horst
通讯作者：
Kunz, Horst
影响因子：
7.3
作者：
Pan, YB;Chefalo, P;Guo, ZW
通讯作者：
Guo, ZW
影响因子：
15
作者：
Demchenko, AV;Wolfert, MA;Boons, GJ
通讯作者：
Boons, GJ