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Question asked in Foot and Mouth Disease2 What's the most effective FMDV vaccine?Foot-and-mouth disease virus
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Article: Recombinant adenovirus expressing type Asia1 foot-and-mouth disease virus capsid proteins induces protective immunity against homologous virus challenge in mice.
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ABSTRACT: Foot-and-mouth disease (FMD) is a highly contagious disease worldwide affecting cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). The FMDV capsid polyprotein and 3C proteinase are required for capsid precursor processing and assembly. The FMDV capsid protein, which contains the entire repertoire of immunogenic sites, can stimulate both humoral immunity and T-cell-mediated immune responses. In this study, we constructed a recombinant adenovirus, rAdV-Asi-05, that expresses the P1-2A and 3C genes of the type Asia1 FMDV strain Asia1/YS/CHA/05. The humoral immune responses elicited by the Ad5-vectored capsid protein of type Asia1 FMDV in BALB/c mice and the ability of rAdV-Asi-05 to rapidly induce protection against challenge with FMDV Asia1/YS/CHA/05 in C57BL/6 mice were evaluated. The processing of polyprotein P1 into the structural proteins VP0, VP3, and VP1 in rAdV-Asi-05-infected HEK 293 cells was detected by Western blotting. BALB/c mice immunised with rAdV-Asi-05 produced type Asia1 FMDV-specific neutralising antibodies, and the neutralisation titres increased significantly after the boost. Importantly, C57BL/6 mice immunised with a single 10(7) PFU dose of rAdV-Asi-05 exhibited protective immunity against challenge with 100 times the lethal dose of FMDV Asia1/YS/CHA/05. In summary, rAdV-Asi-05 elicited a high titre of neutralising antibodies against type Asia1 FMDV in BALB/c mice. Moreover, rAdV-Asi-05 provided complete protection against FMDV Asia1/YS/CHA/05 challenge in C57BL/6 mice. This study highlights the potential of rAdV-Asi-05 to serve as a type Asia1 FMDV vaccine.Research in Veterinary Science 12/2012; · 1.65 Impact Factor -
Article: Effects of amino acid substitutions in the VP2 B-C loop on antigenicity and pathogenicity of serotype Asia1 foot-and-mouth disease virus.
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ABSTRACT: BACKGROUND: Foot-and-mouth disease virus (FMDV) exhibits a high degree of antigenic variability. Studies of the antigenic diversity and determination of amino acid changes involved in this diversity are important to the design of broadly protective new vaccines. Although extensive studies have been carried out to explore the molecular basis of the antigenic variation of serotype O and serotype A FMDV, there are few reports on Asia1 serotype FMDV. METHODS: Two serotype Asia1 viruses, Asia1/YS/CHA/05 and Asia1/1/YZ/CHA/06, which show differential reactivity to the neutralizing monoclonal antibody (nMAb) 1B4, were subjected to sequence comparison. Then a reverse genetics system was used to generate mutant versions of Asia1/YS/CHA/05 followed by comparative analysis of the antigenicity, growth property and pathogenicity in the suckling mice. RESULTS: Three amino acid differences were observed when the structural protein coding sequences of Asia1/1/YZ/CHA/06 were compared to that of Asia1/YS/CHA/05. Site-directed mutagenesis and Immunofluorescence analysis showed that the amino acid substitution in the B-C loop of the VP2 protein at position 72 is responsible for the antigenic difference between the two Asia1 FMDV strains. Furthermore, alignment of the amino acid sequences of VP2 proteins from serotype Asia1 FMDV strains deposited in GenBank revealed that most of the serotype Asia1 FMDV strains contain an Asn residue at position 72 of VP2. Therefore, we constructed a mutant virus carrying an Asp-to-Asn substitution at position 72 and named it rD72N. Our analysis shows that the Asp-to-Asn substitution inhibited the ability of the rD72N virus to react with the MAb 1B4 in immunofluorescence and neutralization assays. In addition, this substitution decreased the growth rate of the virus in BHK-21 cells and decreased the virulence of the virus in suckling mice compared with the Asia1/YS/CHA/05 parental strain. CONCLUSIONS: These results suggest that variations in domains other than the hyper variable VP1 G-H loop (amino acid 140 to 160) are relevant to the antigenic diversity of FMDV. In addition, amino acid substitutions in the VP2 influenced replicative ability and virulence of the virus. Thus, special consideration should be given to the VP2 protein in research on structure-function relationships and in the development of an FMDV vaccine.Virology Journal 09/2012; 9(1):191. · 2.34 Impact Factor -
Article: Adenovirus-vectored type Asia1 foot-and-mouth disease virus (FMDV) capsid proteins as a vehicle to display a conserved, neutralising epitope of type O FMDV.
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ABSTRACT: The objective of this study was to explore the immunogenicity of an adenovirus construction expressing a type O foot and mouth disease virus neutralising epitope (8E8) in the context of heterologous capsid proteins. Adenoviruses expressing four chimeric type Asia1 FMDV capsid proteins were constructed by inserting the type O FMDV 8E8 epitope into the G-H loop from the type Asia1 VP1 at amino acid residues 139/140, 150/151, 134/140 or at both 139/140 and 150/151. These recombinant proteins were recognised by antibodies against the type O 8E8 epitope and type Asia1 FMDV. When inoculated in mice, all of the recombinant chimeric capsid proteins for each single epitope insertion induced the production of anti-type O FMDV neutralising antibodies. The recombinant chimeric capsid proteins with a foreign insertion at position 139/140 or 150/151 induced high levels of anti-type Asia1 FMDV neutralising antibodies as the recombinant type Asia1 capsid proteins without any foreign epitope, suggesting that the foreign insertion did not affect the immunogenicity of the type Asia1 FMDV capsid proteins. This study suggests that a foreign epitope displayed on the surface of the FMDV capsid proteins could induce an epitope-specific response. Therefore, the adenovirus-vectored FMDV capsid proteins could be used as a vehicle for the development of an epitope-based vaccine.Journal of virological methods 09/2012; · 2.13 Impact Factor -
Article: Insertion of type O-conserved neutralizing epitope into the foot-and-mouth disease virus type Asia1 VP1 G-H loop: effect on viral replication and neutralization phenotype.
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ABSTRACT: Previously, we finely mapped the neutralizing epitopes recognized by foot-and-mouth disease virus (FMDV) type Asia1-specific mAb 3E11 and FMDV type O-specific mAb 8E8. In this study, we engineered recombinant FMDVs of the serotype Asia1 (rFMDVs) displaying the type O-neutralizing epitope recognized by the mAb 8E8. These epitope-inserted viruses were genetically stable and exhibited growth properties that were similar to those of their parental virus. Importantly, the recombinant virus rFMDV-C showed neutralization sensitivity to both FMDV type Asia1 and type O mAbs, as well as to polyclonal antibodies. These results indicated that this epitope-inserted virus has the potential to induce neutralizing antibodies against both FMDV type Asia1 and type O. Our results demonstrated that the G-H loop of FMDV type Asia1 effectively displays the protective neutralizing epitopes of other FMDV serotypes, making this an attractive approach for the design of novel FMDV vaccines.Journal of General Virology 04/2012; 93(Pt 7):1442-8. · 3.36 Impact Factor -
Article: Fine mapping of a foot-and-mouth disease virus epitope recognized by serotype-independent monoclonal antibody 4B2.
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ABSTRACT: VP2 is a structural protein of the foot-and-mouth disease virus (FMDV). In this study, a FMDV serotype-in-dependent monoclonal antibody (MAb), 4B2, was generated. By screening a phage-displayed random 12-peptide library, we found positive phages displaying the consensus motif ETTXLE (X is any amino acid (aa)), which is highly homologous to (6)ETTLLE(11) at the N-terminus of the VP2 protein. Subsequently, a series of GST-fusion proteins expressing a truncated N-terminus of VP2 were examined by western blot analysis using the MAb 4B2. The results indicated that the motif (6)ETTLLE(11) of VP2 may be the minimal requirement of the epitope recognized by 4B2. Moreover, a 12-aa peptide (2)KKTEETTLLEDR(13) was shown to be the minimal unit of the epitope with maximal binding activity to 4B2. Alanine-scanning analysis demonstrated thatThr(7), Thr(8), and Leu(10) are the functional residues of the 4B2 epitope Glu(6) and Leu(9) are required residues, and Glu(11) plays a crucial role in the binding of MAb 4B2. The fine mapping of the epitope indicated that MAb 4B2 has the potential to be used in FMDV diagnosis.The Journal of Microbiology 02/2011; 49(1):94-101. · 1.10 Impact Factor
