Baculovirus Strongly Potentiate Antitumor Immune Responses.

PAULA MOLINARI; MARÍA INÉS CRESPO; MARÍA J GRAVISACO; OSCAR TABOGA; GABRIEL MORÓN

Buenos Aires

Congreso; First French-Argentine Immunology Congress y LVIII Reunión Anual de la Sociedad Argentina de Inmunología.; 2010

Sociedad Argentina de Inmunología.

Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They infect a broad range of mammalian cell types but do not replicate in these cells. A recombinant BVs was designed which displays OVA on the capsid as a fusion with vp39 gene (BV-OVA). We previously demonstrated 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 adaptive 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 with BV-OVA on days 7 (i.v., 5x107 BV-OVA), 11 and 17 (s.c., 1x107) and 21 (i.t., 1x107). Additional mouse groups (n=8) received similar schemes of immunization with BV-WT or PBS as control. Mice from the prophylactic protocol injected with PBS or BV-WT developed growing tumors (Survival 0 %, day 32 dpt) whereas BV-OVA mice were free of tumor all along the experiment (Survival 100 %, 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 recombinant BVs is enough to establish a protective immunity against MO5 challenge, showing the potential of BVs as a new strategy of vaccination.