Leishmania nucleoside hydrolase and sterol 24-c-methyltransferase (Leish-F3)

Leishmania nucleoside hydrolase (NH) and sterol 24-c-methyltransferase (SMT) are two highly conserved enzymes essential for the survival and virulence of Leishmania parasites. Nucleoside hydrolase is a key component of the purine salvage pathway, which is vital because Leishmania species are unable to synthesize purines de novo (Coler et al., 2015). Sterol 24-c-methyltransferase is required for the synthesis of ergosterol, the primary sterol in the parasite's cell membrane, and is absent in mammalian hosts, making it an ideal drug and vaccine target (UniProt Q9N9R7). These two proteins are often combined into a recombinant fusion protein known as Leish-F3, which is being developed as a vaccine candidate for visceral and cutaneous leishmaniasis (ClinicalTrials.gov NCT01754324). When formulated with an adjuvant such as GLA-SE, the NH-SMT epitopes trigger a potent Th1-type immune response, characterized by the secretion of interferon-gamma and tumor necrosis factor-alpha by CD4+ T cells (Coler et al., 2015). This immune activation enhances the microbicidal activity of macrophages, leading to the destruction of intracellular amastigotes. The high degree of conservation of these enzymes across different Leishmania species suggests that targeting these epitopes could provide broad protection against multiple forms of the disease.

Other names

Leish-F3NH-SMT fusion proteinNucleoside hydrolase-Sterol 24-c-methyltransferaseLEISH-F3+GLA-SE

The Leish-F3 vaccine, composed of NH and SMT epitopes, acts by inducing a robust Th1-type cellular immune response. Upon administration with the GLA-SE adjuvant, it stimulates CD4+ T cells to produce pro-inflammatory cytokines, including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which activate macrophages to kill intracellular Leishmania amastigotes (Coler et al., 2015).