INVESTIGADORES
RODRIGUEZ Ana Maria
congresos y reuniones científicas
Título:
OPTIMIZATION OF THE MVA VACCINE POTENTIAL AFTER DELETION OF A VIRAL GENE CODING FOR THE IL-18 BINDING PROTEIN
Autor/es:
JULIANA FALIVENE; M.P. DEL MEDICO ZAJAC; ANA MARíA RODRIGUEZ; MARíA FERNANDA PASCUTTI; CYNTHIA MAETO; B PERDIGUERO; C. GOMEZ; M. ESTEBAN; G.CALAMANTE; GHERARDI MM
Lugar:
Bangkok
Reunión:
Conferencia; AIDS Vaccine Conference 2011; 2011
Resumen:
Background: Modified Vaccinia Ankara (MVA) is an attenuated strain of Vaccinia virus (VV) currently employed in many clinical trials against HIV/AIDS. MVA still retains genes involved in host immune response evasion, enabling its optimization by removing some of them. The aim of this work was to evaluate cellular immune responses (CIR) induced by a MVA bearing an IL-18 binding protein gene deletion (MVAÄIL-18bp). Methods: Balb/c and C57Bl/6 mice were immunized with different doses of MVAÄIL-18bp or MVA wild type (MVAwt), then CIR to VV epitopes were evaluated in spleen and draining lymph nodes at acute and memory phases (7 and 40 days post-immunization respectively). The proportion of IFN-gamma and IL-2 producing cells were measured by ELISPOT. The percentage of cytotoxic TCD8+ cells was analyzed by flow cytometry through CD107a/b surface marker. In vivo protection against an intranasal challenge with the replicative Western Reserve (WR) strain was evaluated during the memory phase, measuring the weight of individual Balb/c mice during two weeks. Finally, CIR against HIV-1 antigens expressed from MVA vectors was analyzed by ELISPOT using DNA prime/MVA boost schemes. Results: Compared with MVAwt, MVAÄIL-18bp immunization induced a significant two or three-fold increase in TCD8+ (p<0.01) and TCD4+ (p<0.05) responses to different VV epitopes, and increased the percentage of cytotoxic TCD8+ cells (p<0.05) in the acute phase. Potentiation of MVA’s immunogenicity was also observed in the memory phase, in correlation with a higher protection against an intranasal challenge with WR. More importantly we also observed a significant increase in the CIR against HIV antigens such as Env, Gag, Pol and Nef from different subtypes expressed from MVAÄIL-18bp in DNA prime/MVA boost vaccination regimens. Conclusions: IL-18bp contributes to immune response evasion during MVA infection, as its deletion from the viral genome potentiated the MVA immunogenicity observed against vector antigens and more importantly to HIV antigens.