FLAGELINAS BACTERIANAS PARA MEJORAR RESPUESTA INMUNOLOGICA

Hybrid flagellin as a T cell independent vaccine scaffold

Kaila M. Bennett¹², Ronald D. Gorham³, Veronica Gusti¹, Lien Trinh¹, Dimitrios Morikis³and David D. Lo^1*

• *Corresponding author: David D Lo david.lo@ucr.edu

Author Affiliations

¹Division of Biomedical Sciences, School of Medicine, University of California Riverside, California 92521, USA

²Bioengineering Interdepartmental Graduate Program, California, USA

³Department of Bioengineering, University of California Riverside, California 92521, USA

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BMC Biotechnology 2015, 15:71  doi:10.1186/s12896-015-0194-0

The electronic version of this article is the complete one and can be found online at: VER MAS : http://www.biomedcentral.com/1472-6750/15/71

Received:	1 March 2015
Accepted:	29 July 2015
Published:	12 August 2015

© 2015 Bennett et al. 

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

Background

To extend the potency of vaccines against infectious diseases, vaccines should be able to exploit multiple arms of the immune system. One component of the immune system that is under-used in vaccine design is the subset of B cells known to be capable of responding to repetitive antigenic epitopes and differentiate into plasma cells even in the absence of T cell help (T-independent, TI).

Results

To target vaccine responses from T-independent B cells, we reengineered a bacterial Flagellin (FliC) by replacing its exposed D3 domain with a viral envelope protein from Dengue virus (DENV2). The resulting hybrid FliC protein (hFliC) was able to form stable filaments decorated with conformationally intact DENV2 envelope domains. These filaments were not only capable of inducing a T cell-dependent (TD) humoral antibody response, but also significant IgM and IgG3 antibody response in a helper T cell repertoire-restricted transgenic mouse model.

Conclusions Our results provide proof-of-principle demonstration that a reengineered hybrid FliC could be used as a platform for polymeric subunit vaccines, enhancing T cell-dependent and possibly inducing T-independent antibody responses from B-1 B cells as well. TOMADO DE ENVIO DE BCM