A novel method for synthetic vaccine construction based on protein assembly

Liu, Zhida; Zhou, Hang; Wang, Wenjun; Tan, Wenjie; Fu, Yang-Xin; Zhu, Mingzhao

A successful vaccine is an integral, functional whole composed of different elements. The discovery of effective antigens and immunomodulatory molecules is a major challenge in the field of vaccine development 3, 4 . Modern immunology and genomics provide a large amount of candidates for each. Simple, rapid and efficient experimental screening of the optimal composition of a vaccine is generally in demand, especially when facing pandemic outbreaks of infections, such as SARS-CoV in 2003 25 , H1N1 influenza in 2009 26 and MERS-CoV in 2012 27 . The traditional de novo generation of gene-based synthetic vaccines is both time consuming and costly. In our present study, based on the SpyTag/SpyCatcher technique, we have developed a novel method of vaccine construction by protein assembly based on pre-prepared vaccine components. We have employed this technique for the construction of a DC-targeting vaccine and have found it highly efficient to induce both T-and B-cell responses. Although this strategy still relies on genetic manipulation and protein production, it does not require synthesizing a large, complex fusion protein de novo every time; the strategy only produces smaller protein components as building blocks, which is easier and faster. This block-building strategy may allow people to construct various formulations of vaccines conveniently and efficiently when needed. The approach may simplify the whole process of vaccine generation and accelerate antigen screening and verification ( Figure 6 ). In addition, certain vaccine components (building blocks) may be easily reused for the construction of other vaccines.