Immunogenicity Potential of MVA Vectors after Removal of the Immunomodulatory A44L and A46R Viral Genes

MARIA PIA HOLGADO; FALIVENE JULIANA; M.P. DEL MEDICO ZAJAC; CYNTHIA MAETO; ANA MARÍA RODRIGUEZ; MARÍA FERNANDA PASCUTTI; G.CALAMANTE; GHERARDI MARÍA MAGDALENA

Barcelona

Conferencia; AIDS VACCINE Conference; 2013

Background: 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 (MVAΔA44L-A46R); or with an additional gene deletion: C12L (MVAΔC12L/ΔA44L-A46R). Methods: 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 IFN-γ 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. Results: Compared with MVAwt at 7dpi both dMVAs induced significant increases in the IFN-γ anti-VACV CD8 and CD4-Tcells (1,5 to two-fold, p