Plasmids Encoding Foot-and-Mouth Disease Virus VP1 Epitopes Elicited Immune Responses in Mice and Swine and Protected Swine against Viral Infection

Abstract

VP1 is a capsid protein of foot-and-mouth disease virus (FMDV) and contains epitopes of the virus. Plasmids encoding two VP1 epitopes (amino acid residues 141-160 and 200-213) and a host-self immunoglobulin molecule were constructed to produce a new type of FMD DNA vaccine. Two plasmids, namely, pCEIM and pCEIS, containing mouse immunoglobulin (IgG) or swine IgG were subjected to immunogenicity testing in mice and swine, respectively. In mice administrated pCEIM in the abdomen using a genegun, both FMDV-specific T-cell proliferation and neutralizing antibodies were detected. In swine immunized with pCEIS at the back of the ear, immune responses were achieved after the second administration. Swine showed a T-cell proliferative response with a stimulation index (SI) of up to 8.1 and a neutralizing antibody response that was able to protect suckling mice from 10(2) LD(50) (lethal dose 50) FMDV challenge. To compare the immunogenicity of the DNA-based vaccine candidate, versus the protein-based vaccine candidates, a second group of swine was immunized with the protein F1-scIgG, which was encoded by the plasmid pCEIS. Injection with F1-scIgG elicited a T-cell proliferative response of SI < 1.7 and a neutralizing antibody response that protected suckling mice from up to 10(5) LD(50) FMDV challenge. In the challenge test, three of three swine immunized with pCEIS were fully protected from FMDV challenge.

Foot-and-Mouth Disease

“…Based on information concerning the FMDV capsid structure, including the prominent surface exposure of VP1 and the immunologically important VP1 G-H surface loop, a number of strategies have been employed. Initially these included use of VP1, either isolated from purified virus or produced by recombinant DNA techniques (23,248); the use of VP1-derived peptides (441) or chemically synthesized VP1 peptides (64,127,160,331,352); the use of live vectors expressing VP1 fusion proteins (242,246); inoculation with DNA expressing VP1 epitopes alone (478) or coadministered with DNA encoding IL-2 (479); and use of transgenic plants expressing the entire VP1-coding region or plants infected with a recombinant tobacco mosaic virus expressing VP1 (472,473). All of these strategies present a limited subset of viral immunogens to the vaccinated animal (see "Antigenic variation" above), and although they often induce high titers of neutralizing antibodies, they do not always achieve protection against virus challenge in livestock (127,(326)(327)(328).…”

Construction and immune response characterization of a recombinant pseudorabies virus co-expressing capsid precursor protein (P1) and a multiepitope peptide of foot-and-mouth disease virus in swine

“…Multiepitope-based vaccines have been extensively investigated by some research groups and considered as an effective strategy to develop new generation of vaccine against FMDV [12,22,[28][29][30][31][32][33][34]. Rational molecular design makes the multiepitope peptides to exhibit better immunogenicty [12,22,35].…”

Enhanced immune response of DNA vaccine (VP1-pCDNA) adsorbed on cationic PLG for foot and mouth disease in guinea pigs

“…Protective immune response by immunization with a genetic vaccine was initially demonstrated in mice that underwent intramuscular injection of naked plasmid DNA encoding the internal nucleoprotein of the influenza virus [3]. Immunization using DNA vaccines is an approach that is being widely investigated to protect against a large number of infectious diseases including FMD [4][5][6][7][8][9]. Immunization with plasmid DNA elicits both cell-mediated and humoral immune responses [10][11][12].…”