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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    • "In early trials, the Mayrink's vaccine was a mixture of killed, sonicated promastigotes of L. amazonensis, L. braziliensis, and unknown Leishmania species. Although tested vaccines were safe and immunogenic significant, yet long-lasting protection could not be shown[54]. The immune response and protective efficacy of volunteers vaccinated with BCG plus killed promastigotes of L. mexicana of commercially available vaccine against CL have been claimed maximum in Eucador[55]. "
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    ABSTRACT: Leishmaniasis is an emerging dermal disorder that causes high morbidity and mortality levels with a wide spectrum of clinical complications. Current situation of chemotherapeutic options with some attempts at immunotherapy has remained a dilemma for the treatment of leishmaniasis. Primary precautionary measure which relies on the managed control of the host and sandfly bite prevention is difficult to establish, as the transmission of the disease is manifested by various Leishmania species. Secondary and tertiary prevention is dependent on the medical assistance using clinical guidelines and adequate therapy. However, long course of duration and resistant nature of drugs with pronounced side effects often lead to reduction or cessation of treatment. The aim of this article is to view the current status of chemotherapeutic agents used against leishmaniasis; a review of natural plant extracts exhibiting antileishmanial activities in vitro or in vivo alone or in combination with recommended drugs seeming to validate their use in folk medicine, topical applications of ointments currently used to develop new compounds under trial, substantial efforts in vaccine development and insights about immunoregulation along with the recommendations and guidelines for future perspectives.
    Full-text · Article · Jan 2016 · Asian Pacific Journal of Tropical Disease
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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.
    Full-text · Article · Oct 2014 · Parasitology International
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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.
    Full-text · Article · Jul 2014 · Frontiers in Immunology
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