Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage

Ana Cláudia Pelizon¹ , Douglas R Martins¹ , Sofia FG Zorzella¹ , Ana Paula F Trombone³ , Júlio CC Lorenzi³ , Robson F Carvalho² , Izaíra T Brandão³ , Arlete AM Coelho-Castelo³ , Célio L Silva³ and Alexandrina Sartori¹

¹Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, 18618-000, Brazil

²Department of Morphology, Biosciences Institute, São Paulo State University (UNESP), Botucatu, São Paulo, 18618-000, Brazil

³Department of Biochemistry and Immunology, University of São Paulo (USP), Ribeirão Preto, São Paulo, 14049-900, Brazil

author email corresponding author email

Genetic Vaccines and Therapy 2007, 5:12doi:10.1186/1479-0556-5-12


Published:	29 November 2007

Abstract

Background

Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated.

Methods

Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA.

Results

This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life.

Conclusion

These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection.