Study of induced protection by intranasal immunization with the vaccine containing the SOD-gene of Leishmania amazonensis

• Grant number: 15/13897-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2015
• End date: September 30, 2016
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luiz Felipe Domingues Passero
• Grantee: Júlia Sobral Szemeredi
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

American Tegumentar Leishmanasis (ATL) can be caused by different species, such as L. (L.) amazonensis, L. (V.) braziliensis, L. (V.) guyanesis and L. (L.) shawi. This illness is considered polymorphous by the variety of lesions, being leishmaniotic ulcer the most common injury. The best prophylactic alternative against ATL would be the development of effective vaccines. Recently, our research group evaluated immunogenicity and protective potential of a DNA vaccine containing the iron superoxide dismutase - encoding gene (pVAX-SOD) in ATL. Results showed that this target was immunogenic and partially protected animals from challenge with L. (L.) amazonensis. It has been verified that intranasal immunizations with DNA vaccines frequently increase their effectiveness. Based on these findings, this project aims to immunize BALB/c mice by intranasal route and to evaluate the protective potential of this target in experimental ATL. Iron superoxide dismutase-encoding gene (SOD) from L. (L.) amazonensis will be inserted into bacterial plasmid pVAX1, already licensed for use in humans. BALB/c mice will be immunized three times with the DNA vaccine, at regular intervals of 21 days by intranasal route. Twenty one days after the last dose, mice will be challenged subcutaneously in the footpads with L. (L.) amazonensis promastigotes. Lesion size will be monitored during60 days through weekly measurements using digital micrometer. After euthanasia, parasite burden will be quantified at the skin point of parasite inoculation by limiting-dilution assay. Cellular immune response will be evaluated in the supernatant of mononuclear cells of lymph node stimulated with whole antigen of L. (L.) amazonensis. Circulating IgG1 and IgG2a isotypes will be measured in serum of experimental animals through ELISA. This project aims to contribute to the development of vaccine candidates against ATL. (AU)