Potentiation of the MVA immunogenicity after the deletion of a viral gene coding for the IL-18 binding protein

JULIANA FALIVENE; MARÍA FERNANDA PASCUTTI; ANA MARÍA RODRIGUEZ; M.P. DEL MEDICO ZAJAC; CYNTHIA MAETO; G.CALAMANTE; GHERARDI MM

Buenos Aires

Congreso; 1 Congreso Fanco Argentino de Inmunologia; 2010

SAI-Francia

Modified Vaccinia Ankara (MVA) is an attenuated Vaccinia virus strain currently employed in clinical trials against multiple infection diseases such as HIV/AIDS, Malaria and Tuberculosis. Despite its large loss of genomic regions during the attenuation process, MVA still retains viral genes involved in host immune response evasion, raising the possibility to increase its vaccine potential by removing some of these genes. The aim of this work was to evaluate immune responses induced by a MVA bearing an IL-18 binding protein (IL-18bp) gene deletion (MVAd008) previously generated in our laboratory. Balb/c and C57BL/6 female mice were immunized intraperitoneally with 5E+07 pfu of MVAd008 or wild type (wtMVA) and cellular immune responses were evaluated 7 days post-infection (dpi). The proportion of specific IFN-gamma producing cells was measured by ELISPOT, in Balb/c mice MVAd008 induced a two-fold increase in TCD8+ response to vector epitopes such as E3 peptide compared with wtMVA whereas in C57Bl/6 a three and two-fold increases were detected for the B8R (TCD8+) and E9L (TCD4+) epitopes. The quality of the response was monitored by flow cytometry showing that IL-18bp deletion induced a large proportion of specific IFN-gamma, TNF and CD107a/b (cytotoxicity parameter) TCD8+ cells. Next, the in vivo protection was evaluated 60 dpi through an intranasal challenge with the replicative WR strain (2E+06 pfu). Mice immunized with 1E+06 pfu of wtMVA lost more weight and started to slowly recover on day 7 whereas those immunized with MVAd008 lost less weight and started to quickly recover at day 6. These results suggest that, during MVA infection, IL-18bp expression contributes to immune response evasion and that its deletion from the viral genome increases specific immune responses against vector epitopes. Further investigation is required to see if this increase in MVA immunogenicity will also augment specific responses against foreign antigens such as HIV proteins.