BACULOVIRUS STRONGLY POTENTIATE ANTITUMOR IMMUNE RESPONSES

PAULA MOLINARI; MARÍA INÉS CRESPO; MARÍA JOSÉ GRAVISACO; OSCAR TABOGA; G. MORON

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

SAI

Baculoviruses (BVs) are sdDNA viruses that are pathogenic for insects. They infect a broad range of mammalian cell types but do not replicate in theses cells. A recombinant BVs was designed which displays OVA on the capsid as a fusion with vp39 gene (BV-OVA). We previously demostrated that BVs have strong properties as adjuvants and as vectors for MHC I Ag presentation in mice and promoting potent CD4 and CD8 T cell adaptative responses against OVA. BVs also induce in vitro and in vivo maturation of dendritic cells and the production of inflammatory cytokines. Here we assayed the ability of BV-OVA to induce a protective immune response against a tumor cell challenge. We performed a prophylactic and a therapeutic protection protocol. For the prophylactic protocol, mice (n=8) received a single i.v. injection of 5x107 BV-OVA and seven days later (0 dpt)mice received s.c. 1x105 MO5 cells, a melanoma derived tumor cell stably transfected with the OVA gene. For the therapeutic protocol, mice received s.c. 1x105 MO5 cells and then were injected along the experiment (survival 10 %, p<0.001 for BV-WT or PBS vs BV-OVA). Mice from the therapeutic protocol with PBS or BV-WT developed larger tumors than mice injected with BV-OVA (2.7±1.5 or 3.0±1.4 vs 0.2±0.1 cm3, p<0.001 and p<0.01 ,respectively) at day 25 dpt. Survival was 100 % at day 32 dpt in BV-OVA mice and 0 % in PBS or BV-WT mice (p<0.05 for BV-WT or PBS vs BV-OVA). These results demonstrate that the strong CTL and CD4 T cell response induced by recombinante BVs is enough to establish a protective immunity against MO5 challenge, showing the potential of BVs as a new strategy of vaccination.