Effect of A2 gene on infectivity of the nonpathogenic parasite Leishmania tarentolae

Mizbani, Amir; Taslimi, Yasaman; Zahedifard, Farnaz; Taheri, Tahereh; Rafati, Sima

doi:10.1007/s00436-011-2325-4

Cited by 18 publications

(15 citation statements)

References 34 publications

(42 reference statements)

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“…Conversely, introducing A2 genes into L. major enhanced the ability of L. major –infected cells to migrate out of the dermis and increased parasite survival in visceral organs [10]. Likewise, expression of L. donovani A2 in L. tarentolae (a lizard Leishmania species) enhanced L. tarentolae survival in mouse visceral organs [72]. Finally, A2 expression is downregulated in human post kala-azar dermal leishmaniasis (PKDL) where the L. donovani parasite relocates to the skin following successful treatment [73].…”

Section: Parasite Determinants Of Visceral Leishmaniasismentioning

confidence: 99%

Determinants for the Development of Visceral Leishmaniasis Disease

2013

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Leishmaniasis is a vector-borne neglected tropical disease associated with a spectrum of clinical manifestations, ranging from self-healing cutaneous lesions to fatal visceral infections. Among the most important questions in Leishmania research is why some species like L. donovani infect visceral organs, whereas other species like L. major remain in the skin. The determinants of visceral leishmaniasis are still poorly understood, although genomic, immunologic, and animal models are beginning to provide important insight into this disease. In this review, we discuss the vector, host, and pathogen factors that mediate the development of visceral leishmaniasis. We examine the progression of the parasite from the initial site of sand fly bite to the visceral organs and its ability to survive there. The identification of visceral disease determinants is required to understand disease evolution, to understand visceral organ survival mechanisms, and potentially to develop better interventions for this largely neglected disease.

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Section: Parasite Determinants Of Visceral Leishmaniasismentioning

confidence: 99%

Determinants for the Development of Visceral Leishmaniasis Disease

2013

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“…Further refinement of this approach using recombinant L. tarentolae expressing L. donovani A2 antigen was cross-protective against both L. infantum (Mizbani et al, 2009, 2011) and L. donovani (Yam et al, 2011). Overall, the use of live, non-pathogenic/genetically engineered Leishmania seems to be the most promising strategic alternative against VL.…”

Section: Vl Vaccine Development: New Strategiesmentioning

confidence: 99%

Vaccine Development Against Leishmania donovani

Das¹,

Ali²

2012

Front. Immun.

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Visceral leishmaniasis (VL) caused by Leishmania donovani and Leishmania infantum/chagasi represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Zoonotic VL caused by L. infantum is a re-emergent canid zoonoses which represents a complex epidemiological cycle in the New world where domestic dogs serve as a reservoir host responsible for potentially fatal human infection and where dog culling is the only measure for reservoir control. Life-long immunity to VL has motivated development of prophylactic vaccines against the disease but very few have progressed beyond the experimental stage. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge of pathogenesis, immune response, and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine candidates, their developmental status and future prospects in a quest for rational vaccine development against the disease. In addition, several challenges such as safety issues, renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing prophylactic strategies for protection against this lethal infection.

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“…The multigene family encode a set of 478 Host-microbe interactions: Parasites [65 ]. Furthermore, the A2 is an important virulence factor [66], which is critical in the visceralization process of L. donovani [67][68][69].…”

Section: Protective Immunity and The Development Of Vaccines For Viscmentioning

confidence: 99%