This chapter comprehensively details the advanced engineering and application of virus-like particles (VLPs) utilizing the silkworm expression system. It systematically covers the design and production of both enveloped VLPs (eVLPs) and nonenveloped VLPs (neVLPs). For eVLPs, strategies including genetic fusion and coexpression are explored to develop bivalent and multivalent antigen-displaying platforms, highlighting their potential as targeted delivery vehicles. For neVLPs, the focus shifts to advanced conjugation techniques, particularly SpyTag/SpyCatcher (SpT/SpC) and SnoopTag/SnoopCatcher (SnT/SnC) systems for in vivo and in vitro covalent bonding. The chapter elaborates on rational design approaches to optimize insertion sites within viral structural proteins to enhance the display efficiency. Significant applications are showcased, including the development of bivalent VLPs displaying Plasmodium yoelii malaria antigens and the complex engineering of tetravalent VLPs displaying envelope domain IIIs (EDIIIs) from all four dengue virus serotypes. These engineered VLPs, with their high immunogenicity and precise antigen display, demonstrate the immense potential of silkworm-derived platforms in developing next-generation multivalent vaccines and advanced therapeutics.

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Engineering of Virus-Like Particles (VLPs)

  • Enoch Y. Park

摘要

This chapter comprehensively details the advanced engineering and application of virus-like particles (VLPs) utilizing the silkworm expression system. It systematically covers the design and production of both enveloped VLPs (eVLPs) and nonenveloped VLPs (neVLPs). For eVLPs, strategies including genetic fusion and coexpression are explored to develop bivalent and multivalent antigen-displaying platforms, highlighting their potential as targeted delivery vehicles. For neVLPs, the focus shifts to advanced conjugation techniques, particularly SpyTag/SpyCatcher (SpT/SpC) and SnoopTag/SnoopCatcher (SnT/SnC) systems for in vivo and in vitro covalent bonding. The chapter elaborates on rational design approaches to optimize insertion sites within viral structural proteins to enhance the display efficiency. Significant applications are showcased, including the development of bivalent VLPs displaying Plasmodium yoelii malaria antigens and the complex engineering of tetravalent VLPs displaying envelope domain IIIs (EDIIIs) from all four dengue virus serotypes. These engineered VLPs, with their high immunogenicity and precise antigen display, demonstrate the immense potential of silkworm-derived platforms in developing next-generation multivalent vaccines and advanced therapeutics.