BCG-loaded chitosan microparticles: interaction with macrophages and preliminary in vivo studies

Abstract

The aim of this study was to develop a novel BCG-loaded chitosan vaccine with high association efficiency which can afford efficient interaction with APC and elicit local and Th1-type-specific immune response after intranasal administration. Chitosan-suspended BCG and BCG-loaded chitosan-alginate microparticles were prepared by ionotropic gelation. Interaction with APC was evaluated by fluorescence microscopy using rBCG-GFP. Specific immune responses were evaluated following intranasal immunisation of mice. Cellular uptake was approximately two-fold higher for chitosan-suspended BCG. A single dose of BCG-loaded microparticles or chitosan-suspended BCG by intranasal route improved Th1-type response compared with subcutaneous BCG. Chitosan-suspended BCG originated the highest mucosal response in the lungs by intranasal route. These positive results indicate that the proposed approach of whole live BCG microencapsulation in chitosan-alginate for intranasal immunisation was successful in allowing efficient interaction with APC, while improving the cellular immune response, which is of interest for local immunisation against tuberculosis.

Keywords:

• BCG vaccine
• chitosan
• microencapsulation
• mucosal vaccination

Acknowledgements

The authors would like to thank Prof. Elsa Anes (FFUL) and her team (Dr. David Pires, Dr. Nuno Carmo) for BCG Pasteur strain supply and technical support. The authors thank iMed.ULisboa for financial support (UID/DTP/04138/2013) from Fundação para a Ciência e Tecnologia (FCT), Portugal, and Escola Superior de Tecnologia da Saúde de Lisboa for financial support from merit scholarship for Ph.D. (ESTeSL-IPL/CGD/2012) granted by Caixa Geral de Depósitos, Portugal.

Disclosure statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Additional information

Funding

The authors thank iMed.ULisboa for financial support (UID/DTP/04138/2013) from Fundação para a Ciência e Tecnologia (FCT), Portugal, and Escola Superior de Tecnologia da Saúde de Lisboa for financial support from merit scholarship for Ph.D. (ESTeSL-IPL/CGD/2012) granted by Caixa Geral de Depósitos, Portugal.