title: Orally delivered foot-and-mouth disease virus capsid protomer vaccine displayed on T4 bacteriophage surface: 100% protection from potency challenge in mice.
abstract: An orally delivered foot-and-mouth disease (FMD) vaccine has not previously been reported. By using a T4 bacteriophage nanoparticle surface gene-protein display system (T4-S-GPDS), we created a foot-and-mouth disease virus (FMDV) entire capsid protein vaccine candidate. On the T4 phage surface SOC site, a full length FMDV capsid precursor polyprotein (P1, 755 aa) and proteinase 3C (213 aa) derived from an infected pig of serotype O strain GD-10 (1999), were separately displayed on different T4 phage particle surfaces through inserting their coding region DNAs into the T4 phage genome, yielding phage strains T4-P1 and T4-3C. We also constructed a series of FMDV sub-full length capsid structural protein (subunit) containing T4 phage recombinant vaccines. Both sucking and young BALB/c mice were used as two kinds of FMDV vaccine potency evaluation models. Many groups of both model mice were vaccinated orally or by subcutaneous injection with varying FMDV-T4 phage recombinant vaccines, with and without addition of adjuvant, then challenged with a lethal dose of cattle source virulent FMDV. In the case of immunization with a mixture of phage T4-P1 and phage T4-3C particles without any adjuvant added, all mice were 100% protected following either oral or injection immunization, whereas 100% of the control, non-immunized mice and mice immunized with only T4 phage vector Z1/Zh(-) or wild-type T4(+)D phage died; in contrast, with FMDV subunit vaccine, less than 75% protection followed the same potency challenge in both mice model groups. In addition, two pigs immunized with a phage T4-P1 and phage T4-3C mix were protected upon housing together with infected pigs. This study represents a clear example of how FMD and other pathogenic disease vaccines can be prepared by a simple and efficient bacteriophage route.
authors.affiliation: Expression BioSciences Inc., Somerset, NJ 08873, USA. renzhaojun@yahoo.com
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Ren
authors.forename: C J
authors.initials: CJ
authors.lastname: Tian
authors.forename: Q S
authors.initials: QS
authors.lastname: Zhu
authors.forename: M Y
authors.initials: MY
authors.lastname: Zhao
authors.forename: A G
authors.initials: AG
authors.lastname: Xin
authors.forename: W X
authors.initials: WX
authors.lastname: Nie
authors.forename: S R
authors.initials: SR
authors.lastname: Ling
authors.forename: M W
authors.initials: MW
authors.lastname: Zhu
authors.forename: J Y
authors.initials: JY
authors.lastname: Wu
authors.forename: H Y
authors.initials: HY
authors.lastname: Lan
authors.forename: Y C
authors.initials: YC
authors.lastname: Cao
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Bi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017122:Bacteriophage T4 / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000648:ultrastructure / Q000821:virology; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D019151:Peptide Library; D011401:Promoter Regions, Genetic / Q000235:genetics; D015202:Protein Engineering; D012703:Serotyping; D013552:Swine; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D019151:Peptide Library; D014614:Vaccines, Synthetic; D014765:Viral Vaccines