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新型简单缀合化学方法用于 GMMA 异源抗原的修饰。

Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens.

机构信息

GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy.

出版信息

Int J Mol Sci. 2021 Sep 22;22(19):10180. doi: 10.3390/ijms221910180.

DOI:10.3390/ijms221910180
PMID:34638530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8508390/
Abstract

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.

摘要

外膜囊泡 (OMV) 是开发高效疫苗的有前途的平台。OMV 可以用异源抗原（蛋白质或多糖）进行修饰，成为开发多组分疫苗的有吸引力的新型载体。化学偶联代表了将抗原（甚至来自系统发育上不同的病原体）连接到 OMV 的工具。在这里，我们开发了两种针对表面的通用模块膜抗原（GMMA）上的蛋白质或脂多糖的简单且广泛适用的偶联化学方法，从增加囊泡产量和降低潜在反应原性的突变革兰氏阴性细菌中自发释放 OMV。实验设计方法用于在偶联之前确定 GMMA 激活的最佳条件，从而实现一致的过程并确保偶联效率。两种化学方法产生的缀合物均针对异源抗原和 GMMA 诱导了强烈的体液反应。此外，两种正交化学方法的使用允许控制相同 GMMA 颗粒上两个不同抗原的连接。这项工作支持进一步推进这一具有巨大潜力的新型平台，用于设计有效的疫苗。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4511/8508390/d8287c2ffccc/ijms-22-10180-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4511/8508390/5d6acf44aafb/ijms-22-10180-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4511/8508390/64d64bd69720/ijms-22-10180-g008.jpg
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