A novel method for synthetic vaccine construction based on protein assembly

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

S ince the creation of the first vaccine, for cowpox, by Edward Jenner in the late eighteenth century 1 , immunological research on vaccines has focused on deconstruction analysis, or evaluation of the importance and mechanisms of each component of a vaccine that may determine its effect. This research strategy has led to the discovery of a large, increasing number of functional elements of different categories including antigens, immune modulators and adjuvants, and delivery systems, among others 2 . A successful vaccine is usually composed of multiple elements, such as those listed above. Given the multitude of choices, the construction of different elements into an integrated, functional whole has become a new challenge in the field. Although genebased synthetic and recombinant DNA technologies provide great flexibility for construction, certain limitations still exist: (1) large fusion proteins containing multiple functional elements are occasionally technically difficult to express or purify, and (2) de novo generation is usually a tedious and long process that is especially inadequate in the face of emergent pandemics of infectious diseases, when screening and identification of antigens are crucial for vaccine development 3, 4 . Facing such difficulties and demands, instead of making complex fusion-protein candidate vaccines de novo every time, it would be easier, faster, more flexible and more efficient to prepare the smaller building blocks first and then to assemble them into a whole, as needed.