Immunization withLeishmania majorExogenous Antigens Protects Susceptible BALB/c Mice against Challenge Infection withL. major

Abstract

The potential of Leishmania major culture-derived soluble exogenous antigens (SEAgs) to induce a protective response in susceptible BALB/c mice challenged with L. major promastigotes was investigated. Groups of BALB/c mice were immunized with L. major SEAgs alone, L. major SEAgs coadministered with either alum (aluminum hydroxide gel) or recombinant murine interleukin-12 (rmIL-12), L. major SEAgs coadministered with both alum and rmIL-12, and L. major SEAgs coadministered with Montanide ISA 720. Importantly and surprisingly, the greatest and most consistent protection against challenge with L. major was seen in mice immunized with L. major SEAgs alone, in the absence of any adjuvant. Mice immunized with L. major SEAgs had significantly smaller lesions that at times contained more than 100-fold fewer parasites. When lymphoid cells from L. major SEAg-immunized mice were stimulated with leishmanial antigen in vitro, they proliferated and secreted a mixed profile of type 1 and type 2 cytokines. Finally, analyses with Western blot analyses and antibodies against three surface-expressed and secreted molecules of L. major (lipophosphoglycan, gp46/M2/ PSA-2, and gp63) revealed that two of these molecules are present in L. major SEAgs, lipophosphoglycan and the molecules that associate with it and gp46/M2/PSA-2.

Protein Expression Profiling of Coccidioides posadasii by Two-Dimensional Differential In-Gel Electrophoresis and Evaluation of a Newly Recognized Peroxisomal Matrix Protein as a Recombinant Vaccine Candidate

“…Infection in humans and animals is initiated when an arthroconidium is inhaled into the respiratory tract. Subsequently, in the lung, arthroconidia develop into thickwalled, spore-filled structures known as spherules, presumably with significant changes in the protein expression profile of the organism (12,24,49). Spherule development can be replicated in vitro by growing arthroconidia under conditions of elevated temperature and CO 2 (8).…”

“…Moreover, protective antigens derived from Coccidioides spp. have been either cell wall associated or actively secreted from spherules (1,13), similar to effective subcellular immunogens in vaccines against other pathogens (23,32,49). An additional theoretical characteristic of a protective antigen for any pathogen is that it be directly virulence associated, e.g., an adhesin or immunomodulatory protein, specifically expressed during the infectious phase (2,25,31,35,48).…”

Subcutaneous immunization against Leishmania major - infection in mice: efficacy of formalin-killed promastigotes combined with adjuvants

“…Aluminium salts are inexpensive, safe and simple to formulate (BOMFORD, 1989). Alum has been previously used in leishmania candidate vaccines alone or in combination with other adjuvants (KENNEY et al, 1999;MISRA et al, 2001;TONUI et al, 2004). Montanide ISA 720 (MISA 720) has been recommended by the manufacturer for clinical trials in humans (GOMEZ et al, 1999 as an adjuvant is regarded as an acceptable practice in humans, and at present this adjuvant is routinely used in vaccination and immunotherapy trials against leishmaniasis (CONVIT et al, 1989;BAHAR et al, 1996;SHARIFI et al, 1998;MOMENI et al, 1999;KHALIL et al, 2000).…”

“…The number of adjuvants currently approved for use in humans is quite limited and of those adjuvants that have been tested in humans, alum has had the greatest clinical use and is relatively nonreactogenic (KASLOW et al, 1994). Alum is currently the only Food and Drug Administration-approved adjuvant in clinical use in humans (TONUI et al, 2004). Aluminium salts are inexpensive, safe and simple to formulate (BOMFORD, 1989).…”

Vaccinations with live-attenuated <i>Leishmania major</i> promastigotes and challenge infection with <i>L. major</i> in balb/c mice

“…Lymphocyte proliferation assays: Lymphocytes were obtained from mice spleens as previously described (15). Spleens from immunised animals or control groups were aseptically crushed on a wire mesh using a syringe plunger and mononuclear cells were separate using Ficoll gradients.…”