Immunoinformatics Approach to Design a Multi-Epitope Nanovaccine against Leishmania Parasite: Elicitation of Cellular Immune Responses

Abstract

Leishmaniasis is a vector-borne disease caused by an intracellular parasite of the genus Leishmania with different clinical manifestations that affect millions of people worldwide, while the visceral form may be fatal if left untreated. Since the available chemotherapeutic agents are not satisfactory, vaccination emerges as the most promising strategy for confronting leishmaniasis. In the present study, a reverse vaccinology approach was adopted to design a pipeline starting from proteome analysis of three different Leishmania species and ending with the selection of a pool of MHCI- and MHCII-binding epitopes. Epitopes from five parasite proteins were retrieved and fused to construct a multi-epitope chimeric protein, named LeishChim. Immunoinformatics analyses indicated that LeishChim was a stable, non-allergenic and immunogenic protein that could bind strongly onto MHCI and MHCII molecules, suggesting it as a potentially safe and effective vaccine candidate. Preclinical evaluation validated the in silico prediction, since the LeishChim protein, encapsulated simultaneously with monophosphoryl lipid A (MPLA) into poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles, elicited specific cellular immune responses when administered to BALB/c mice. These were characterized by the development of memory CD4+ T cells, as well as IFNγ- and TNFα-producing CD4+ and CD8+ T cells, supporting the potential of LeishChim as a vaccine candidate.

Development of a multi-epitope vaccine candidate for leishmanial parasites applying immunoinformatics and in vitro approaches

“…Host immune responses are primarily regulated by various immune cell types that secrete multiple cytokines and chemokines, which interconnect inflammatory and immune responses (Th1 and Th2) against microorganisms that cause infections ( 62 ). Here, Ld MAPV was found to significantly increase TNF-α, IL-1β, IL-6, and IL-12 cytokines that was in accordance with previous studies where in silico designed multi-epitope vaccines for VL were effective in inducing immunogenicity by upregulating the pro-inflammatory cytokines such as IFN-γ and TNF-α ( 63 , 64 ). Similarly, in accordance to the previous report ( 64 ), lower level of IL-10 (anti-inflammatory cytokine) was observed suggesting potential induction of Th1 type immune response through designed vaccine.…”

“…Here, Ld MAPV was found to significantly increase TNF-α, IL-1β, IL-6, and IL-12 cytokines that was in accordance with previous studies where in silico designed multi-epitope vaccines for VL were effective in inducing immunogenicity by upregulating the pro-inflammatory cytokines such as IFN-γ and TNF-α ( 63 , 64 ). Similarly, in accordance to the previous report ( 64 ), lower level of IL-10 (anti-inflammatory cytokine) was observed suggesting potential induction of Th1 type immune response through designed vaccine. Nitric oxide (NO) is a critical effector molecule derived from immune cells that functions as a toxic agent against many noxious infections, including leishmaniasis, trypanosomiasis, malaria, and toxoplasmosis ( 65 ).…”

Designing of a multi-epitopes based vaccine against Haemophilius parainfluenzae and its validation through integrated computational approaches

“…The purpose of this phase was to assess the sequence’s ability to elicit an immunological response. Using the ProtParam service, the modified vaccine’s physicochemical characteristics were ascertained ( 44 ). These properties included:…”

Scoping Review of Deep Learning Techniques for Diagnosis, Drug Discovery, and Vaccine Development in Leishmaniasis

“…These vaccines are designed to provide broad protection by integrating multiple epitopes from different Leishmania antigens into a single vaccine construct. Here are some of the tools and approaches used to develop vaccine targets against multiepitope leishmaniasis [112][113][114]:…”