Research

Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs

Lúcia de Paula¹ , Célio L Silva² , Daniela Carlos¹ , Camila Matias-Peres¹ , Carlos A Sorgi¹ , Edson G Soares³ , Patrícia RM Souza² , Carlos RZ Bladés² , Fábio CS Galleti⁴ , Vânia LD Bonato² , Eduardo DC Gonçalves⁴ , Érika VG Silva¹ and Lúcia H Faccioli¹

¹  Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903, Ribeirão Preto, SP, Brasil

²  NPT – Núcleo de Pesquisas em Tuberculose – Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brasil

³  Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, SP, Brasil

⁴  Farmacore Biotecnologia Ltda, Rua dos Técnicos s/n, Campus da USP – Ribeirão Preto, SP, Brasil

author email corresponding author email

Genetic Vaccines and Therapy 2007, 5:2doi:10.1186/1479-0556-5-2

Published:	24 January 2007

Abstract

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs.