Brucella spp. lumazine synthase as a Bovine Rotavirus antigen delivery system

BELLIDO, D., CRAIG, P. O., MOZGOVOJ, M. V., GONZALEZ, D. D., WIGDOROVITZ, A., GOLDBAUM, F. A. AND DUS SANTOS, M. J.

VACCINE

ELSEVIER SCI LTD

Año: 2009 vol. 27 p. 136 - 145

0264-410X

<!-- /* Font Definitions */ @font-face {font-family:Verdana; panose-1:2 11 6 4 3 5 4 4 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:536871559 0 0 0 415 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Verdana; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:EN-GB; mso-fareast-language:ES;} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} --> Brucella spp lumazine synthase (BLS) presents a very resistent and high order decameryc structure. It allows the fusion of peptides in its 10 N-terminus, giving chimeric proteins with high order arrangement that are able to induce efficient immune responses. Bovine Rotavirus (BRV) VP8 protein is an accurate protein to be fused to BLS based on its physical, chemical and immunological properties. In this work, we fused the bovine rotavirus VP8 core protein to the structure of BLS with the aim to: (i) test the feasibility of using BLS as an antigen delivery system of protein antigens larger in size compared to those previously tested, (ii) produce an enhancement of the immune response against BVR VP8, (iii) analyze the capability of the chimeric protein to induce passive protection against BVR, and (iv) evaluate the possible use of this antigen for vaccine development. Groups of female mice were immunized with BLS-VP8 (fusion protein), VP8 and BLS+VP8 (without fusion). Dams immunized with the chimeric protein (BLS-VP8) induced 100% protection; while, pups born to dams immunized either with VP8d nor VP8+BLS (without fusion) presented a significant lower level of protection. The neutralizing antibody pattern was also significatly different in these experimental groups, and in concordance with challenge experiment. Overall, our results demonstrate that the VP8d-BLS chimeric protein is properly folded and stable, and that the BLS scaffold is a potent antigen delivery system that enhances the antibody response against BVR and elicits a complete homotypic passive protection in a suckling mice model