Vaccination of BALB/c mice withLeishmania majoramastigote-specific cysteine proteinase

Abstract

SUMMARYCellular immune mechanisms resulting in interferon-gamma (IFN-g) production are essential for protection against cutaneous leishmaniasis. Antigens of the intracellular amastigote form of the parasite, found in mammalian hosts, are likely to be good candidates for the induction of T cell response and protection from development of leishmaniasis. We purified a stage-specific antigen from amastigote soluble antigen (A-SLA) of Leishmania major by immunoaffinity chromatography. The purified protein was characterized as a cysteine proteinase with enzymatic activity which is inhibited by E-64, and it was named the amastigote cysteine proteinase (ACP). BALB/c mice were immunized by two intraperitoneal injections, at a month interval, of 5 m g of ACP or A-SLA in Freund's complete adjuvant (FCA). Animals were challenged 4 weeks later with 10 6 L. major promastigotes and examined 4 months after the last injection. The immunized animals developed significantly smaller or no lesions compared with controls. Spleen cells from immunized mice showed a significant proliferative response and produced a high level of IFN-g in response to ACP, suggesting the induction of Th1 cells after immunization. These results make 24-kD ACP a possible component for an eventual cocktail vaccine against L. major infection.

In SituImmunolocalization and Stage-Dependent Expression of a Secretory Serine Protease inLeishmania donovaniand Its Role as a Vaccine Candidate

“…The mechanism of protection is currently unknown, and work is in progress to find out the basis of this protection. It could be due to an increase in the Th1/Th2 ratio, since several workers have reported that protective immunity in response to vaccination is associated with an increased Th1 response (12,28). Immunomodulatory cytokines might also be involved in eliciting the immune protection (12,28).…”

Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4+T Cells

“…Killed or live attenuated parasites, as well as a large number of leishmanial antigens from different species, have been identified and tested as vaccines. Studies of recombinant protein vaccines in mice demonstrated that antigens such as the proteins GP63, p36/LACK, A-2, PSA-2, and KMP11 induced strong immune responses but weak and short-lived protection against Leishmania infection (1,3,29,35,38,39). Other studies have identified several antigens, including lmd29 and 584C, that reproducibly exacerbated leishmania disease (37).…”

Leishmania chagasiT-Cell Antigens Identified through a Double Library Screen

“…There are many reports of antigens expressed by the promastigote (insect) stage of Leishmania that are recognized by the mammalian immune system (34). Some studies focus on antigens that are highly expressed in the intracellular amastigote, the stage present throughout mammalian infection (23,25,44,49,59). This report documents our systematic screen of an L. chagasi amastigote cDNA library to identify T-cell and T-cell-dependent B-cell antigens expressed in the mammalian parasite form.…”