Brucella spp. lumazine synthase as a bovine rotavirus antigen delivery system.
Brucella spp. lumazine synthase (BLS) is a highly immunogenic decameric protein. It has been previously evaluated as a carrier to increase the immunogenicity of peptides fused to its N-termini. VP8 is a sialic acid binding domain of rotavirus external capsid protein VP4, which is involved in virus adhesion to host cells. In this work, the C486 bovine rotavirus (BRV) VP8 core protein (VP8d) was fused to the structure of BLS with the aim to produce an enhancement of the immune response against BRV VP8 and to evaluate the possible use of this antigen for vaccine development. The feasibility of using BLS as an antigen delivery system of polypeptides larger in size than those previously tested was also evaluated. Groups of female mice were immunized with BLS-VP8d fusion protein, VP8d or an equimolar mixture of purified VP8d and BLS (BLS+VP8d). Dams immunized with BLS-VP8 induced 97.5-100% protection against homologous challenge with C486 BRV; while pups born to dams immunized either with VP8d or BLS+VP8d presented a significant lower level of protection. The neutralizing antibody pattern was also significantly different among these experimental groups, and in concordance with challenge experiment. Overall, these results demonstrate that the BLS-VP8d chimeric protein is properly folded and stable, and that the BLS scaffold is a potent antigen delivery system that enhances the antibody response against BRV and elicits complete homotypic passive protection in a suckling mouse model.
Bellido
Demian
D
Instituto de Virología S. Rivenson, Centro de Investigaciones en Ciencias Veterinarias, INTA Castelar, Buenos Aires, Argentina.
Craig
Patricio O
PO
Mozgovoj
Marina V
MV
Gonzalez
Diego D
DD
Wigdorovitz
Andrés
A
Goldbaum
Fernando A
FA
Dus Santos
María José
MJ
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D002002:Brucella / Q000201:enzymology* / Q000276:immunology; D002417:Cattle; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012401:Rotavirus / Q000737:chemistry* / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D011993:Recombinant Fusion Proteins; D022243:Rotavirus Vaccines; D014614:Vaccines, Synthetic