**5. Baculovirus and cellular immunity**

Apart from infecting insect cells, baculoviruses are able to transduce different types of animal cells such as human, rodent, rabbit, porcine, bovine, fish and avian cells (Hu, 2005; Hu, 2006) In addition, baculovirus can transduce embryonic stem cells, adult stem cells and induced pluripotent stem cells (Chen et al., 2011).

Baculovirus are safer than other transduction vectors because they don´t integrate its DNA into host genome, nor replicates it inside the transduced cells (Chen et al., 2011; Merrihew et al., 2001). It has been demonstrated that humans do not possess pre-existing antibodies and specific T-cells against baculoviruses (Strauss et al., 2007). For this reason, baculoviruses may avoid the pre-existing immunity problem caused by other viral vectors.

Thus, the coding sequence of a protein of interest can be cloned into the viral genome under the control of a suitable promoter. Then, the inoculation of an animal with the recombinant virus results in the expression of the heterologous protein inside different cell types. The expression of a foreign protein in the cytoplasm trigger the MHC class I antigen presentation of proteasome processed peptides of the recombinant protein. In this way, joined to the adjuvancy showed by baculoviruses, transduction of animal cells may induce a strong cellular immune response (Figure 4.c).

Yoshida et al. have developed a baculovirus based dual expression system, with the aim to develop multifunctional vaccines capable of inducing strong humoral and cellular immune responses. In this study a chimeric protein was constructed with the display necessary sequences of Gp64 and the entire open reading frame of the*Plasmodium berghei* circumsporo‐ zoite protein (PbCSP) under the control of polyhedron and CMV Ie1 promoters. ELISPOT assays with splenocytes from immunized mice with the recombinant baculovirus showed significative IFN-γ secretion compared with the results for immunization with a recombinant AcMNPV without the CMV Ie1 promoter when the splenocytes was stimulated with a PbCSP synthetic peptide. In addition, this baculovirus based dual system showed to be more protec‐ tive than the simple baculovirus display system (Yoshida et al., 2009)

On the other hand, Hervas-Stubbs et al. demonstrated that baculoviruses induced strong humoral and cellular immune responses by co-administration of AcMNPV wt. and a purified antigen.They showed that budded baculoviruses had strong adjuvant properties, promoting humoral and CTL responses against coadministered antigen. They observed also that baculo‐ virus could induced DC maturation, and the production of inflammatory mediators through mechanisms primarily mediated by IFN-α and IFN-β.It has been shown previously that type I IFNs act directly on naive B cells and CD4+ and CD8+ T cells, promoting clonal expansion and differentiation (Curtinsger 2005; (Bon & Lucchetti, 2006).
