Immune Responses Induced by theLeishmania(Leishmania)donovaniA2 Antigen, but Not by the LACK Antigen, Are Protective against ExperimentalLeishmania(Leishmania)amazonensisInfection

Abstract

Leishmania amazonensis is one of the major etiologic agents of a broad spectrum of clinical forms of leishmaniasis and has a wide geographical distribution in the Americas, which overlaps with the areas of transmission of many other Leishmania species. The LACK and A2 antigens are shared by various Leishmania species. A2 was previously shown to induce a potent Th1 immune response and protection against L. donovani infection in BALB/c mice. LACK is effective against L. major infection, but no significant protection against L. donovani infection was observed, in spite of the induction of a potent Th1 immune response. In an attempt to select candidate antigens for an American leishmaniasis vaccine, we investigated the protective effect of these recombinant antigens (rLACK and rA2) and recombinant interleukin-12 (rIL-12) against L. amazonensis infection in BALB/c mice. As expected, immunization with either rA2-rIL-12 or rLACK-rIL-12 induced a robust Th1 response prior to infection. However, only the BALB/c mice immunized with rA2-rIL-12 were protected against infection. Sustained gamma interferon (IFN-γ) production, high levels of anti-A2 antibodies, and low levels of parasite-specific antibodies were detected in these mice after infection. In contrast, mice immunized with rLACK-rIL-12 displayed decreased levels of IFN-γ and high levels of both anti-LACK and parasite-specific antibodies. Curiously, the association between rA2 and rLACK antigens in the same vaccine completely inhibited the rA2-specific IFN-γ and humoral responses and, consequently, the protective effect of the rA2 antigen against L. amazonensis infection. We concluded that A2, but not LACK, fits the requirements for a safe vaccine against American leishmaniasis

Proteoliposomes in nanobiotechnology

“…Several Leishmania proteins have been identified, and the most comprehensively studied antigens include glycoprotein 63 (gp63) (Xu et al 1995;Bhowmick et al 2008), glycoprotein 46 (gp46) or parasite surface antigen 2 (PSA-2) (McMahon-Pratt et al 1992, 1993, Leishmania homologue of receptors for activated C kinase (LACK) (Coelho et al 2003;Pinto et al 2004), and focused mannose ligand (FML) (Palatnik de Sousa et al 1994;). …”

Novel targeting using nanoparticles: an approach to the development of an effective anti-leishmanial drug-delivery system

“…In this study, a pH of nearly 2.0 was used with a 2% acetic acid solution to dilute the AmpB in aqueous media. 41,42 So as to be successfully incorporated into the system, AmpB should be first solubilized, thus, in this study, a pH of 2.0 in aqueous media was used. This strategy was employed because a net charge on the molecule of AmpB, obtained in acid aqueous media, could increase the solubility in two ways: first, it could decrease the dimerization and association constants by ten-fold or more and, second, it could increase the threshold of degree of aggregation for which oligomers are soluble in water.…”

Recent updates and perspectives on approaches for the development of vaccines against visceral leishmaniasis

“…It is encoded by a multigene family that is abundantly expressed in the amastigote forms of some Leishmania species able to cause VL (40) . Studies of the administration of recombinant A2 protein associated with immune adjuvants (41) (42) or as a DNA vaccine (43) , as well as in attenuated non-replicative viruses (44) , non-pathogenic bacteria (45) , or non-virulent Leishmania tarentolae (46) , have provided evidence of its protective effi cacy in mammalian models. In general, anti-A2 protective immunity is associated with the generation of parasite-specifi c IgG2a antibodies, as well as with the production of high levels of antileishmanial IFN-γ and low levels of IL-10 by T cells in recall response to the A2 protein or parasite extracts (40) .…”

“…It has been postulated that a formulation containing different Leishmania proteins expressed in both parasite stages should provide better results, in terms of a more effective and protective vaccine against VL (42) (55) . The use of vaccines combining different proteins could provide the benefi ts of increased simplicity and reduced production costs, since it would only be necessary to produce a single vaccine to protect against different Leishmania species (56) .…”