Analysis of the deletion of three viral genes from MVA genome related with host immune response evasion: effect on its immunogenicity against VACV epitopes.

HOLGADO, M.P.; FALIVENE, J.; DEL MÉDICO ZAJAC, M.P.; PASCUTTI, M.F.; MAETO, C.A.; RODRͬGUEZ, A.M.; CALAMANTE, G.; GHERARDI, M.M.

Los Cocos, Cordoba

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología.; 2013

Sociedad Argentina de Inmunología.

Modified Vaccinia Ankara (MVA) still retains genes involved in host immune response evasion. We have previously reported the optimization of MVA vaccine potential after the deletion of the C12L gene encoding an IL-18 binding protein. Here we analyze the immunogenicity of MVA vectors harboring the simultaneous deletion of two viral genes: A44L, implicated in synthesis of steroid hormones and A46R, which inhibit transduction signals from TLR receptors (MVAdA44L-A46R); or with an additional gene deletion: C12L (MVAdC12L/dA44L-A46R). C57Bl/6 mice were intramuscularly immunized with wild type (MVAwt), or deleted MVAs (dMVAs). T-cell responses to VACV (Vaccinia Virus) epitopes were evaluated at acute and memory phases (7 and 45 days post-immunization (dpi) respectively). The proportion of IFNg and IL-2 producing cells was measured by ELISPOT. Percentage of cytotoxic CD8-T cells was analyzed by flow citometry through CD107a/b surface-marker, and memory T-cell responses by expression of CD44 and CD62L among proliferating (CFSElow) T-cell populations. Compared with MVAwt at 7dpi both dMVAs induced significant increases in the IFNg anti-VACV CD8 and CD4-T cells (1,5 to two-fold, p