Non PC liposome entrapped promastigote antigens elicit parasite specific CD8+ and CD4+ T-cell immune response and protect hamsters against visceral leishmaniasis

摘要

Leishmania donovani promastigote soluble antigens (sLAg) were encapsulated in non-phosphatidylcholine (non-PC) liposomes (escheriosomes) prepared from E. coli lipids. The escheriosome-based vaccine was investigated for its potential to elicit a protective immune response against experimental visceral leishmaniasis. The vaccine administration induced strong humoral as well as cell mediated immune responses both in hamsters and BALB/c mice. Immunization of BALB/c mice with escheriosome entrapped sLAg (EL-sLAg) elicited stronger CD8+ cytotoxic T lymphocyte (CTL) response as compared to sLAg entrapped in egg PC/chol liposome (EPC-sLAg) or sLAg administered with incomplete Freund's adjuvant (IFA-sLAg). EL-sLAg also induced the release of mixed (Th1 and Th2) types of cytokines in the immunized BALB/c mice. In addition, the delivery of sLAg via escheriosomes enhanced the expression of costimulatory signals (CD80 and CD86) as determined in peritoneal macrophages obtained from BALB/c mice. In another set of experiments, the EL-sLAg immunized hamsters were found to be better protected than those immunized with EPC-sLAg. The prophylaxis coincided with increased lymphocyte proliferation as well as high nitric oxide (NO) production by peritoneal macrophages among EL-sLAg immunized hamsters. Escheriosomes thus seem to have potential in delivering the antigen to cytosol of the antigen presenting cells (APCs) and in the development of liposome-based vaccine against leishmaniasis as well as other intracellular infections.