Immunotherapy and immunochemotherapy in combating visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL), a vector-borne disease, is caused by an obligate intramacrophage, kinetoplastid protozoan parasite of the genus Leishmania. Globally, VL is construed of diversity and complexity concerned with high fatality in tropics, subtropics, and Mediterranean regions with ~50,000–90,000 new cases annually. Factors such as the unavailability of licensed vaccine(s), insubstantial measures to control vectors, and unrestrained surge of drug-resistant parasites and HIV-VL co-infections lead to difficulty in VL treatment and control. Furthermore, VL treatment, which encompasses several problems including limited efficacy, emanation of drug-resistant parasites, exorbitant therapy, and exigency of hospitalization until the completion of treatment, further exacerbates disease severity. Therefore, there is an urgent need for the development of safe and efficacious therapies to control and eliminate this devastating disease. In such a scenario, biotherapy/immunotherapy against VL can become an alternative strategy with limited side effects and no or nominal chance of drug resistance. An extensive understanding of pathogenesis and immunological events that ensue during VL infection is vital for the development of immunotherapeutic strategies against VL. Immunotherapy alone or in combination with standard anti-leishmanial chemotherapeutic agents (immunochemotherapy) has shown better therapeutic outcomes in preclinical studies. This review extensively addresses VL treatment with an emphasis on immunotherapy or immunochemotherapeutic strategies to improve therapeutic outcomes as an alternative to conventional chemotherapy.

The Future of Leishmaniasis Treatment: Protein Targets and Beyond

“…Currently, standard active compounds used against Leishmania parasites include Amphotericin B, Miltefosine, Pentamidine, Antimonials, Paromomycin, Sitamaquine, Pamidronate, Azoles, and 3 of 29 Nucleoside analogues. [30][31][32][33][34][35][36], However, these drugs often demonstrate inefficiency and high toxicity in patients undergoing clinical treatments. The effectiveness and toxicity of these drugs depend on various factors, such as the immunological state of the infected host and the pharmacokinetic properties of the drugs themselves.…”

Acrylonitrile derivatives: In vitro activity and mechanism of cell death induction against Trypanosoma cruzi and Leishmania amazonensis

“…In addition, other strategies such as the combination of drugs with immunotherapy have shown encouraging results. Within this group we can highlight rldccys1, a recombinant cysteine protease from Leishmania , or the use of L. braziliensis antigens with saponin and monophosphoryl lipid-A ( Yadagiri et al, 2023 ). Similarly, there has been an increase in the number of studies related to the search for new therapies against Chagas disease.…”

Synthetic biology for combating leishmaniasis

“…When L. donovani -infected mice were treated with a single dose of anti-IL-10R monoclonal antibody, Sb(V) and amphotericin individually, the percentage of parasites killed in the liver increased to approximately 63, 72, and 76%, respectively ( Figure 1A ; Sasidharan and Saudagar, 2021 ). One major barrier preventing the development and use of cytokine immunotherapy as therapeutic and vaccine is the unification of innate and acquired immunity together with the unavailability of information on the human immune response ( Yadagiri et al, 2023 ).…”