Identifying vaccine targets for anti-leishmanial vaccine development

Sundar, Shyam; Singh, Bhawana

doi:10.1586/14760584.2014.894467

Cited by 46 publications

(37 citation statements)

References 173 publications

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“…Like many parasitic infections, CL has the ability to induce little immune stimulation through the continuous variation of antigenic epitopes and immunosuppressive mechanisms [ 98 ]. These immune-evasive characteristics impose a serious challenge on the development of an effective CL vaccine [ 99 ].…”

Section: Preventionmentioning

confidence: 99%

Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management

2015

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This review focuses on recent developments in the diagnosis, treatment, management, and strategies for the prevention and control of cutaneous leishmaniasis (CL) caused by both Old and New World Leishmania species. CL is caused by the vector-borne protozoan parasite Leishmania and is transmitted via infected female sandflies. The disease is endemic in more than 98 countries and an estimated 350 million people are at risk. The overall prevalence is 12 million cases and the annual incidence is 2–2.5 million. The World Health Organization considers CL a severely neglected disease and a category 1 emerging and uncontrolled disease. The management of CL differs from region to region and is primarily based on local experience-based evidence. Most CL patients can be treated with topical treatments, but some Leishmania species can cause mucocutaneous involvement requiring a systemic therapeutic approach. Moreover, Leishmania species can vary in their sensitivity to available therapeutic options. This makes species determination critical for the choice of treatment and the clinical outcome of CL. Identification of the infecting parasite used to be laborious, but now the Leishmania species can be identified relatively easy with new DNA techniques that enable a more rational therapy choice. Current treatment guidelines for CL are based on poorly designed and reported trials. There is a lack of evidence for potentially beneficial treatments, a desperate need for large well-conducted studies, and standardization of future trials. Moreover, intensified research programs to improve vector control, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are needed.

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Section: Preventionmentioning

confidence: 99%

Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management

2015

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“…Leishmania infection occurs in over 88 countries, with an estimated 12 million people currently infected and over 350 million people at risk (11)(12)(13). The parasitic infection is spread by the sand fly, primarily impacting people in resource-strained settings.…”

mentioning

confidence: 99%

Intradermal Synthetic DNA Vaccination Generates Leishmania -Specific T Cells in the Skin and Protection against Leishmania major

et al. 2019

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Vaccination remains one of the greatest medical breakthroughs in human history and has resulted in the near eradication of many formerly lethal diseases in many countries, including the complete eradication of smallpox. However, there remain a number of diseases for which there are no or only partially effective vaccines. There are numerous hurdles in vaccine development, of which knowing the appropriate immune response to target is one of them. Recently, tissue-resident T cells have been shown to mediate high levels of protection for several infections, although the best way to induce these cells is still unclear. Here we compare the ability to generate skin-resident T cells in sites distant from the immunization site following intramuscular and intradermal injection using optimized synthetic DNA vaccines. We found that mice immunized intradermally with a synthetic consensus DNA HIV envelope vaccine by electroporation (EP) are better able to maintain durable antigen-specific cellular responses in the skin than mice immunized by the intramuscular route. We extended these studies by delivering a synthetic DNA vaccine encoding Leishmania glycosomal phosphoenolpyruvate carboxykinase (PEPCK) by EP and again found that the intradermal route was superior to the intramuscular route for generating skin-resident PEPCK-specific T cells. We observed that when challenged with Leishmania major parasites, mice immunized intradermally exhibited significant protection, while mice immunized intramuscularly did not. The protection seen in intradermally vaccinated mice supports the viability of this platform not only to generate skin-resident T cells but also to promote durable protective immune responses at relevant tissue sites.

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“…Leishmania sirtuins from L. major and L. infantum have demonstrated roles in parasite growth in vitro and in vivo. Involvement of the protein in parasite virulence and survival [11, 12] suggests that it may be exploited as a novel vaccine target against leishmaniasis [43]. Recombinant SIR2 protein was reported to be capable of inducing the activation and differentiation of B cells, thus producing specific antibodies [44], and demonstrated a protective function in BALB/c mice by reducing the parasite load after L. infantum infection [45].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and protective efficacy of silent information regulator 2A from Eimeria tenella

et al. 2016

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BackgroundSilent information regulator 2 (SIR2) proteins are a family of NAD + -dependent protein deacetylases that are considered potential targets for anti-parasitic agents. In this study, we cloned and characterized SIR2A of the protozoan parasite Eimeria tenella (EtSIR2A) and investigated its protective efficacy as a DNA vaccine.MethodsThe EtSIR2A gene encoding 33.37 kDa protein from E. tenella second-generation merozoites was cloned, and recombinant EtSIR2A protein (rEtSIR2A) was produced in an Escherichia coli expression system. The rEtSIR2A was used to immunize rabbits. Anti-rEtSIR2A antibodies were used to determine the immunolocolization of EtSIR2A in the parasite by immunofluorescence assay (IFA). Transcript and protein expression of EtSIR2A in different development stages of E. tenella were observed by quantitative real-time PCR (qPCR) and western blot (WB) analysis, respectively. The recombinant plasmid pCAGGS-EtSIR2A was constructed and its efficacy against E. tenella infection in chickens was evaluated.ResultsqPCR and WB analysis revealed EtSIR2A expression was developmentally regulated at both the mRNA and protein levels. EtSIR2A mRNA levels were higher in unsporulated oocysts than at other developmental stages, including sporulated oocysts, sporozoites and second-generation merozoites. In contrast, EtSIR2A protein expression levels were highest in second-generation merozoites, moderate in unsporulated oocysts and sporulated oocysts and lowest in sporozoites. Immunostaining with anti-rEtSIR2A antibody indicated that EtSIR2A was mainly located in the cytoplasm of sporozoites and second-generation merozoites, and was strongly expressed during first stage schizogony. Animal-challenge experiments demonstrated that immunization with pCAGGS-EtSIR2A significantly increased average body-weight gain, and decreased mean lesion score and oocyst output in chickens.ConclusionsThese results suggest that EtSIR2A may play an important role in parasite cell survival and may be an effective candidate for the development of new vaccines against E. tenella infection in chickens.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1871-0) contains supplementary material, which is available to authorized users.

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Identifying vaccine targets for anti-leishmanial vaccine development

Cited by 46 publications

References 173 publications

Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management

Cutaneous Leishmaniasis: Recent Developments in Diagnosis and Management

Intradermal Synthetic DNA Vaccination Generates Leishmania -Specific T Cells in the Skin and Protection against Leishmania major

Molecular characterization and protective efficacy of silent information regulator 2A from Eimeria tenella

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