Leishmania Immunity: Advancing Immunotherapy and Vaccine Development

Abstract

Parasitic diseases still constitute a major global health problem affecting billions of people around the world. These diseases are capable of becoming chronic and result in high morbidity and mortality. Worldwide, millions of people die each year from parasitic diseases, with the bulk of those deaths resulting from parasitic protozoan infections. Leishmaniasis, which is a disease caused by over 20 species of the protozoan parasite belonging to the genus Leishmania, is an important neglected disease. According to the World Health Organization (WHO), an estimated 12 million people are currently infected in about 98 countries and about 2 million new cases occur yearly, resulting in about 50,000 deaths each year. Current treatment methods for leishmaniasis are not very effective and often have significant side effects. In this review, we discussed host immunity to leishmaniasis, various treatment options currently being utilized, and the progress of both immunotherapy and vaccine development strategies used so far in leishmaniasis. We concluded with insights into what the future holds toward the fight against this debilitating parasitic disease.

Designing of a Novel Fusion Protein Vaccine Candidate Against Human Visceral Leishmaniasis (VL) Using Immunoinformatics and Structural Approaches

“…Advanced tools based on bioinformatics and immunoinformatic methods are used to develop and design a vaccine that reduces the negative aspects of empirical methods, including preventing predictable ethical aspects of laboratory works and expensive experimental studies and being time consuming. In order to control VL, it is essential to stimulate both humoral and particularly cellular immune responses (Poland and Oberg 2010 ; Ghorbani and Farhoudi 2018 ; Farhani et al 2019 ; Ahmadi et al 2020 ; Ikeogu, Akaluka et al 2020 ; Mahboobi, Sedighian et al 2020 ; Oli, Obialor et al 2020 ). The humoral immune response, providing antibodies, is an essential part of the design of vaccines.…”

Visualizing the In Vivo Dynamics of Anti-Leishmania Immunity: Discoveries and Challenges

“…A more recent study demonstrated that L. donovani can directly activate B cells via endosomal TLR stimulation, proposing a novel parasite-driven survival mechanism by inducing hypergammaglobulinemia and increased levels of type I interferons, both associated with immune suppression and disease pathology (75) (Figure 2D). This study highlights the potential role B cells play in exacerbating disease, but this is still controversial, as both pathogenic and protective roles of B cells to other forms of Leishmaniasis have been described (72). Antibodies and serum are not protective against leishmaniasis (73,76), and when donor CD4 + T cells are transferred into irradiated Balb/c mice lacking B cells, they become resistant to Leishmania tropica infection (77).…”

“…B cell responses are considered to play a minor role in anti- Leishmania immunity and have been mostly studied in the context of cutaneous leishmaniasis in vivo ( 72 , 73 ). However, in visceral leishmaniasis, Moore et al demonstrated that highly motile B cells are present in L. donovani granulomas in the liver, irrespective of their antigen specificity or their capacity to interact with the intra-granuloma T cells ( 74 ).…”

Identification of 3-Methoxycarpachromene and Masticadienonic Acid as New Target Inhibitors against Trypanothione Reductase from Leishmania Infantum Using Molecular Docking and ADMET Prediction

“…A paramount public health concern, it is endemic in 98 countries. Approximately 2 million new cases are registered annually, with about 50,000 deaths each year [ 3 ]. Two epidemiological forms, cutaneous and visceral leishmaniasis, are diffuse in Algeria, which has the second-highest prevalence of cutaneous leishmaniasis ranks, after Afghanistan [ 4 ].…”