KSAC, a Defined Leishmania Antigen, plus Adjuvant Protects against the Virulence of L. major Transmitted by Its Natural Vector Phlebotomus duboscqi

Leishmaniasis is a neglected disease caused by the Leishmania parasite and transmitted by the bite of an infective sand fly. Despite the importance of this disease there is no vaccine available for humans. Studies have shown that vector-transmitted infections are more virulent, promoting parasite establishment and abrogating protection observed against needle-injected parasites in vaccinated mice. KSAC and L110f, derived from Leishmania-based polyproteins, protected mice against the needle-injected parasites. Here, we tested the two molecules for their capacity to protect mice against cutaneous leishmaniasis transmitted by an infective sand fly. Our results show that KSAC, but not L110f, confers protection against Leishmania transmitted by sand fly bites where protection was correlated to a strong immune response to Leishmania antigens by memory T cells before and after sand fly transmission of the parasite. This is the first report of a Leishmania-based vaccine that confers protection against a virulent sand fly challenge. Our results support the importance of screening Leishmania vaccine candidates using infective sand flies before moving forward with the costly steps of vaccine development

2-Hydroxymethyl-3,4-dihydroxy-6-methyl-pyrrolidine (6-deoxy-DMDP), an alkaloid beta-mannosidase inhibitor from seeds of Angylocalyx pynaertii.

A polyhydroxy alkaloid has been isolated from the seeds of the African legume Angylocalyx pynaertii and identified as a 2-hydroxymethyl-3,4-dihydroxy-5-methylpyrrolidine by ms and 1H- and 13C-nmr spectroscopy. The absolute stereochemistry was established, by a stereochemically unambiguous synthesis from diacetone glucose, as 2,5-imino-1,2,5-trideoxy-D-mannitol, which may also be regarded as 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine (DMDP) [2] in which a hydroxymethyl group is deoxygenated, i.e., 6-deoxy-DMDP [1]. Whereas the structurally related polyhydroxypyrrolidine alkaloids which have previously been discovered are inhibitors of alpha- and beta-glucosidase, 6-deoxy-DMDP is unique in inhibiting beta-mannosidase. In addition to this novel alkaloid and 2-hydroxymethyl-3,4-dihydroxypyrrolidine [3], previously shown to be present in several Angylocalyx species, the known piperidine alkaloids deoxymannojirimycin [4] and fagomine [5] were identified for the first time as constituents of An. pynaertii seeds