Orally delivered foot-and-mouth disease virus capsid protomer vaccine displayed on T4 bacteriophage surface: 100% protection from potency challenge in mice

• Published in: Vaccine Vol. 26; no. 11; pp. 1471 - 1481
• Main Authors: Ren, Z.J, Tian, C.J, Zhu, Q.S, Zhao, M.Y, Xin, A.G, Nie, W.X, Ling, S.R, Zhu, M.W, Wu, J.Y, Lan, H.Y, Cao, Y.C, Bi, Y.Z
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 10.03.2008; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Animals, Newborn; Applied microbiology; Bacteria; Bacteriophage T4; Bacteriophage T4 - immunology; Biological and medical sciences; Capsid - immunology; Deoxyribonucleic acid; DNA; DNA, Viral - biosynthesis; DNA, Viral - genetics; DNA, Viral - immunology; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Escherichia coli - ultrastructure; Escherichia coli - virology; FMDV; Foot & mouth disease; Foot-and-Mouth Disease - immunology; Foot-and-Mouth Disease - prevention & control; Foot-and-Mouth Disease - virology; Foot-and-mouth disease virus; Foot-and-Mouth Disease Virus - genetics; Foot-and-Mouth Disease Virus - immunology; Foot-and-Mouth Disease Virus - pathogenicity; Fundamental and applied biological sciences. Psychology; Immunization; Injections, Subcutaneous; Male; Mice; Mice, Inbred BALB C; Microbiology; Microscopy, Electron; Miscellaneous; Peptide Library; Phage T4 platform vaccine; Plasmids; Potency challenge; Promoter Regions, Genetic - genetics; Protein Engineering; Proteins; Serotyping; Swine; T4 phage surface gene-protein display system; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - therapeutic use; Viral Vaccines - immunology; Virology; FMDV; T4 phage surface gene-protein display system; Phage T4 platform vaccine; Bacteriophage T4; Potency challenge; Picornaviridae; Rodentia; Vaccine; Myoviridae; Protein; Virus; Aphthovirus; T even phage; Vertebrata; Phage display; Mammalia; Gene; Mouse; Veterinary; Capsid; Phage; Phage T4
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.12.053

Summary 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.