Studies on immunology of Leishmania mexicana

• Main Author: Rezvan, Hossein
• Published: Nottingham Trent University 2007
• Subjects: 616.9364; Protozoan parasites
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493096

Leishmaniasis is a worldwide disease prevalent in many tropical and sub tropical countries. Treatment of Leishmaniasis by chemotherapy is not wholly effective and is usually accompanied by unpleasant side effects. The development of an effective and inexpensive vaccine represents a practical way to control the disease, however at present no safe and effective vaccine is available. In the first part of the present study, the immunity induced by four different L. mexicana potential vaccines, including killed leishmania vaccine, Soluble L. mexicana Antigen (SLA), L. mexicana gp63 cDNA and CT26 tumour cells transfected with L. mexicana gp63, were compared. It was shown that DNA immunisation using L. mexicana gp63 generated the highest immunity to the parasite among the four tested vaccines where the killed leishmania vaccine and L. mexicana gp63 transfected CT26 tumour cells did not generate significant immunity. The efficacy of DNA immunisation by intramuscular injection or using gene gun, in generating immunity to leishmania was compared. Gene gun immunisation induced more immunity to the parasite and high levels of Th1 immune response, which were detected, one week after immunisation through determination of the IgG2a levels in blood serum. Gene gun immunisation also induced long-lasting CTL activity, which was detectable before and during the course of infection for up to 6 months. Immunogenicity of MHC class I restricted peptides derived from L. mexicana gp63 have been investigated. Using 'SYFPEITHI' software, four peptides with high affinity to human HLA-A2 and four peptides with high affinity to mouse H2-Ld were predicted, synthesized and tested in HHD II and BALB/c mice respectively. Only three of the peptides predicted with high affinity to HLA-A2 were immunogenic but only two of them were likely to be naturally processed, however, none were protective in HHD II mice against leishmania infection. Purification and application of OX40L, a ligand for T-cell co-stimulatory receptor, was investigated in L. mexicana BALB/c model. In addition to purification by protein A sepharose, the murine OX40L-IgG fusion protein produced by B9B8E2 cells (cells transfected with OX40L and IgG) was successfully purified by two novel resins, MBI & MEP. The biological activity of the OX40L-IgG purified by MBI resin was significantly higher than that of MEP or protein A sepharose resins. Application of OX40L-IgG resulted in healing of leishmania lesions or delaying in development of the lesions in leishmania-infected mice.