Second-generation vaccines against leishmaniasis. Trends Parasitol

The Infectious Disease Research Institute, 1124 Columbia Street, Suite 600, Seattle, WA 98104, USA.
Trends in Parasitology (Impact Factor: 6.2). 06/2005; 21(5):244-9. DOI: 10.1016/
Source: PubMed


Several species of Leishmania cause human diseases that range from self-healing cutaneous lesions to fatal visceral leishmaniasis, mucosal leishmaniasis and diffuse cutaneous leishmaniasis. Drug resistance and toxicities associated with chemotherapy emphasize the need for a safe, effective vaccine. Studies of the immunopathogenesis and mechanisms of protective immunity define several features that should be met by an effective vaccine. The leishmaniases are unique among parasitic diseases because a single vaccine has the potential to protect against more than one species (disease) and be successful at both treating and preventing disease. In addition, several antigens have been identified and characterized that might be potential vaccine candidates. In this article, we focus on advances made with second-generation vaccines against leishmaniasis.

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    • "It is a Th1 promoting adjuvant [25] [26]. Formulations of adjuvant based on MPL have been evaluated in various clinical trials with vaccines against malaria [27], tuberculosis [28], leishmaniasis [29] and cancer [30]. These studies have established the safety and efficacy of this promising adjuvant. "
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    ABSTRACT: Despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. Killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to the lack of an appropriate adjuvant. Addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. So, present study was done to evaluate the effectiveness of four adjuvants i.e. alum, saponin, cationic liposomes and Monophosphoryl lipid-A in combination with Autoclaved Leishmania donovani (ALD) antigen against murine visceral leishmaniasis (VL). BALB/c mice were immunized thrice with respective vaccine formulation. Two weeks after last booster, challenge infection was given. Mice were sacrificed 15days after last immunization and on 30, 60 and 90 post infection/challenge days. A considerable protective efficacy was shown by all vaccine formulations. It was evident from significant reduction in parasite load, profound delayed type hypersensitivity responses (DTH), increased IgG2a titres and high levels of Th1 cytokines (IFN-γ, IL-12) as compared to the infected controls. However, level of protection varied with the type of adjuvant used. Maximum protection was achieved with the use of liposome encapsulated ALD antigen and it was closely followed by group immunized with ALD+MPL-A. Significant results were also obtained with ALD+saponin, ALD+alum and ALD antigen (alone) but the protective efficacy was reduced as compared to other immunized groups. The present study reveals greater efficacy of two vaccine formulations i.e. ALD+liposome and ALD+MPL-A against murine VL.
    Parasitology International 10/2014; 64(1). DOI:10.1016/j.parint.2014.10.003 · 1.86 Impact Factor
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    • "Though, whole parasite vaccine (either live/killed or attenuated one) offered vast array of antigens to the host immune system that induced both protective as well as non-protective responses (94), recent advent in our knowledge about the immunobiology of the Leishmania infection provided probable explanations for the failure of the first generation vaccines, which further insisted for the development of newer vaccination strategies against VL. A variety of different molecules were identified from parasite based on their abundance, surface localization, T-cell clones, screening of antigen pools/expression libraries with sera of infected animals and humans, which was further evaluated as suitable vaccine candidates leading to the production of a number of experimental vaccines against different forms of leishmaniasis over past few decades (95). In case of VL, extensive vaccination studies have not been possible due to unavailability of an appropriate animal model. "
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    ABSTRACT: Visceral Leishmaniasis (VL) or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that nearly 500,000 new cases of VL occur annually, including 100,000 cases from India itself. Treatment with available anti-leishmanial drugs are not cost effective, with varied efficacies and higher relapse rate, which poses a major challenge to current kala-azar control program in Indian subcontinent. Therefore, a vaccine against VL is imperative and knowing the fact that recovered individuals developed lifelong immunity against re-infection, it is feasible. Vaccine development program, though time taking, has recently gained momentum with the emergence of omic era i.e. from genomics to immunomics. Classical as well as molecular methodologies has been overtaken with alternative strategies wherein proteomics based knowledge combined with computational techniques (immunoinformatics) speed up the identification and detailed characterization of new antigens for potential vaccine candidates. This may eventually help in the designing of polyvalent synthetic and recombinant chimeric vaccines as an effective intervention measures to control the disease in endemic areas. This review focuses on such newer approaches being utilized for vaccine development against VL.
    Frontiers in Immunology 07/2014; DOI:10.3389/fimmu.2014.00380
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    • "For human use, subunit vaccines based on selected parasite antigens, however, would offer a more defined and more stable alternative (20). But, major obstacles to their successful development exist and these are on the one hand the identification of the most effective antigens and on the other hand their formulation. "
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    ABSTRACT: Visceral leishmaniasis is a neglected infectious disease caused primarily by Leishmania donovani and Leishmania infantum protozoan parasites. A significant number of infections take a fatal course. Drug therapy is available but still costly and parasites resistant to first line drugs are observed. Despite many years of trial no commercial vaccine is available to date. However, development of a cost effective, needle-independent vaccine remains a high priority. Reverse vaccinology has attracted much attention since the term has been coined and the approach tested by Rappuoli and colleagues. This in silico selection of antigens from genomic and proteomic data sets was also adapted to aim at developing an anti-Leishmania vaccine. Here, an analysis of the efforts is attempted and the challenges to be overcome by these endeavors are discussed. Strategies that led to successful identification of antigens will be illustrated. Furthermore, these efforts are viewed in the context of anticipated modes of action of effective anti-Leishmania immune responses to highlight possible advantages and shortcomings.
    Frontiers in Immunology 06/2014; 5:260. DOI:10.3389/fimmu.2014.00260
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