A micro-electroporation/electrophoresis-based vaccine screening system reveals the impact of vaccination orders on cross-protective immunity

Yongyong Li,Jingshan Mo,Jing Liu,Ying Liang,Caiguanxi Deng,Zhangping Huang,Juan Jiang,Ming Liu,Xinmin Liu,Liru Shang,Xiafeng Wang,Xi Xie,Ji Wang

Published 2023 in iScience

ABSTRACT

Summary The constant emergence of mutated pathogens poses great challenges to the existing vaccine system. A screening system is needed to screen for antigen designs and vaccination strategies capable of inducing cross-protective immunity. Herein, we report a screening system based on DNA vaccines and a micro-electroporation/electrophoresis system (MEES), which greatly improved the efficacy of DNA vaccines, elevating humoral and cellular immune responses by over 400- and 35-fold respectively. Eighteen vaccination strategies were screened simultaneously by sequential immunization with vaccines derived from wildtype (WT) SARS-CoV-2, Delta, or Omicron BA.1 variant. Sequential vaccination of BA.1-WT-Delta vaccines with MEES induced potent neutralizing antibodies against all three viral strains and BA.5 variant, demonstrating that cross-protective immunity against future mutants can be successfully induced by existing strain-derived vaccines when a proper combination and order of sequential vaccination are used. Our screening system could be used for fast-seeking vaccination strategies for emerging pathogens in the future.

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