Expression and Immunogenicity of Two Recombinant Fusion Proteins Comprising Foot-and-Mouth Disease Virus Structural Protein VP1 and DC-SIGN-Binding Glycoproteins

Abstract

Improving vaccine immunogenicity by targeting antigens to dendritic cells has recently emerged as a new design strategy in vaccine development. In this study, the VP1 gene of foot-and-mouth disease virus (FMDV) serotype A was fused with the gene encoding human immunodeficiency virus (HIV) membrane glycoprotein gp120 or C2-V3 domain of hepatitis C virus (HCV) envelope glycoprotein E2, both of which are DC-SIGN-binding glycoproteins. After codon optimization, the VP1 protein and the two recombinant VP1-gp120 and VP1-E2 fusion proteins were expressed in Sf9 insect cells using the insect cell-baculovirus expression system. Western blotting showed that the VP1 protein and two recombinant VP1-gp120 and VP1-E2 fusion proteins were correctly expressed in the Sf9 insect cells and had good reactogenicity. Guinea pigs were then immunized with the purified proteins, and the resulting humoral and cellular immune responses were analyzed. The VP1-gp120 and VP1-E2 fusion proteins induced significantly higher specific anti-FMDV antibody levels than the VP1 protein and stronger cell-mediated immune responses. This study provides a new perspective for the development of novel FMDV subunit vaccines.

Advanced Foot-And-Mouth Disease Vaccine Platform for Stimulation of Simultaneous Cellular and Humoral Immune Responses

“…Currently, FMD vaccine studies using an inactivated vaccine, modified virus inactivated vaccine (DIVA vaccine) [ 24 ], viral vector vaccine [ 25 ], adenovirus [ 26 , 27 , 28 ], virus-like particle (VLP) vaccine (bacterial) [ 29 ], baculovirus [ 30 , 31 ], plant-produced empty capsids [ 32 , 33 ], peptide vaccine (Poly(I:C)) [ 34 ], CpG [ 35 ], plant based recombinant vaccine (alfalfa [ 36 ], chloroplast of tobacco [ 37 ]), RNA vaccine [ 38 ], DNA vaccine (cDNA [ 39 , 40 ], electroporation [ 41 ], T cell [ 42 , 43 , 44 ], B cell [ 45 , 46 ] epitope, APC targeting [ 47 ]), live attenuated vaccine [ 48 , 49 , 50 , 51 ], and antiviral agent [ 52 , 53 ] are underway. However, no high-quality FMD vaccines that surpass the efficacy of the inactivated vaccine have been successfully developed to date.…”