Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines
Since the outbreak of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the end of 2019,it has evolved into different lineages,including Alpha,Beta,Delta,and Omicron.The development of broad-spectrum vaccines has become a necessity for preventing the highly mutated respiratory viruses.Traditional vaccine antigens,originating from prototype strains,cannot cover rapid mutations with these viruses,leading to breakthrough infections.With the development of synthetic biology,new technologies such as multivalent coupling of antigens,reconstructed dominate antigen modules,engineering design of conserved epitopes,epitope display,and computation-guided reconstruction have enabled redesigning antigens to achieve stronger immunogenicity with broader spectrum.The technology of synthetic biology is also applicable in the vaccine production process,such as antigen expression in nanoparticles,viral vectors,nucleic acids,and subunits.This article reviews the applications of synthetic biology technology in developing broad-spectrum vaccines in recent years,particularly for the broad-spectrum SARS-CoV-2 vaccines,and summarizes how to display common antigens and cross-antigenic sites by the reverse vaccinology for the activation of broad-spectrum immune responses against different mutant strains,achieving broad-spectrum vaccine protection effects through"remaining constant in response to ever-changing".The article also provides a comprehensive comparison of the strengths and limitations of different broad-spectrum vaccine design strategies and discusses challenges to applying synthetic biology in the development of vaccines,offering valuable insights for universal against highly mutation viruses.