Abstract
BackgroundFoot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance.ResultsThe present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes.ConclusionsSome amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China.
Highlights
Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide
The present study describes the generation of an infectious cDNA clone of foot-and-mouth disease virus (FMDV) O/HN/CHA/93 vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic site 1 (VP1 134 C ! S, 137 S ! G, 139 A ! T, 140 R ! S, 142 V ! T, 142 S ! N), site 3 (VP1 43 T ! K, 48 I ! V), and site 4 (VP3 58 E ! D), based on the established infectious clone
Amino acid variation of FMDV isolates of CHY topotype Deduced amino acid sequence alignments were performed with the data for each isolates of CHY topotype using SeqMan II
Summary
Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. The FMD virion consists of a single-stranded RNA genome packaged in an icosahedrally symmetric protein shell, which is composed of 60 copies each of four structural proteins 1A (VP4), 1B (VP2), 1 C (VP3) and 1D (VP1) [5]. Three of these proteins, VP1, VP2 and VP3, contribute to the formation of five known antigenic sites of type O FMDV [6,7]. The G-H loop and carboxy terminus of VP1 contribute to site 1, key residues have been shown to be 144, 148, 154 and 208, respectively. While much of the antibody response to FMDV can be directed at the G-H loop of VP1, all of the sites appear to be necessary for a complete immunologic response to either infection or vaccination [8,9]
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