Recombinant baculoviruses as vehicles for presentation and adjuvancy of antigens for the development of new TB candidate vaccines

PAULA MOLINARI; VERONICA BIANCO; ANDREA PERALTA; ANGEL CATALDI; FABIANA BIGI; OSCAR TABOGA

Boston, MA, USA

Congreso; 2nd Vaccine Congress; 2008

ASM

The baculovirus (BV) has discovered to be capable of efficiently transducing wide variable mammalian cells, thus leading to the emergence of BV as a novel vector for in vivo and in vitro gene delivery. Recent studies have shown adjuvant properties of BV by enhancing and modulating the immune response in mammals. This ability has been explained in part by the activation of the innate immunity. In addition, BV induced a vigorous type I CTL response characterized by a large number of IFNg-producing cells. By flow cytometry analysis, we demonstrated that, when inoculated in mice, wild type BV induces the production of very high level of IFNg by NK cells. Furthermore, BV-stimulation of splenic cells from mice inoculated with BV induced expansion of CD4+ IFNg-producing cells. Effective immune responses against tuberculosis infection are believed to primarily rely on the development of a T helper type 1 (Th1)-biased CMI response. By manipulating the genome of BV via homologous recombination it is possible to display multiple copies of heterologous polypeptides in the surface in a multimeric way. So, the same particle could act as multimeric antigen presentation structure and a potent adjuvant. Here we developed a recombinant BV by engeeniering its genome in order to display polypeptide 85A from Mycobacterium tuberculosis in the surface of baculovirus. Thus, we combined the immunogenic advantages of BVs and the antigenic features of the antigen 85A for the development of novel tuberculosis vaccine candidate.