Vaccination with whole-cell killed or recombinant leishmanial protein and toll-like receptor agonists against Leishmania tropica in BALB/c mice

Abstract

One strategy to control leishmaniasis is vaccination with potent antigens alongside suitable adjuvants. The use of toll-like receptor (TLR) agonists as adjuvants is a promising approach in Leishmania vaccine research. Leishmania (L.) tropica is among the less-investigated Leishmania species and a causative agent of cutaneous and sometimes visceral leishmaniasis with no approved vaccine against it. In the present study, we assessed the adjuvant effects of a TLR4 agonist, monophosphoryl lipid A (MPL) and a TLR7/8 agonist, R848 beside two different types of Leishmania vaccine candidates; namely, whole-cell soluble L. tropica antigen (SLA) and recombinant L. tropica stress-inducible protein-1 (LtSTI1). BALB/c mice were vaccinated three times by the antigens (SLA or LtSTI1) with MPL or R848 and then were challenged by L. tropica. Delayed-type hypersensitivity (DTH), parasite load, disease progression and cytokines (IL-10 and IFN-γ) responses were assessed. In general compared to SLA, application of LtSTI1 resulted in higher DTH, higher IFN-γ response and lower lymph node parasite load. Also compared to R848, MPL as an adjuvant resulted in higher DTH and lower lymph node parasite load. Although, no outstanding ability for SLA and R848 in evoking immune responses of BALB/c mice against L. tropica infection could be observed, our data suggest that LtSTI1 and MPL have a better potential to control L. tropica infection and could be pursued for the development of effective vaccination strategies.

Fasciola hepatica Extracellular Vesicles isolated from excretory-secretory products using a gravity flow method modulate dendritic cell phenotype and activity

“…hepatica ES antigens [ 80 ]. Finally, in human vaccine development a new generation of TLR-based adjuvants licensed for use such as MPL (3-O-desacyl-4-monophosohryl lipid A), a detoxified bacterial lipopolysaccharide in aluminium salts, could be a promising source of novel adjuvants in veterinary vaccines [ 81 ].…”

“…Similarly, naltrexone, an opioid receptor antagonist that can shift the immune response toward a Th1 profile induced strong protective Th1 immune responses in mice when administered with alum and F. hepatica ES antigens [80]. Finally, in human vaccine development a new generation of TLR-based adjuvants licensed for use such as MPL (3-O-desacyl-4-monophosohryl lipid A), a detoxified bacterial lipopolysaccharide in aluminium salts, could be a promising source of novel adjuvants in veterinary vaccines [81].…”

Investigating the Existence of Ribosomal Protein L5 Gene in Syrian Strain of Leishmania tropica Genome: Sequencing It and Evaluating Its Immune Response as DNA Vaccine

“…Some studies demonstrated that certain strains of L. tropica cause mild pathogenesis in BALB/c mice characterized by small or no detectable swelling in the injection site, so measuring lesion size was not considered as a promising tool for the evaluation of vaccine efficiency as discussed by Fate-meh et al [17] and Rostamian et al [29]. In fact, in some cases, cutaneous lesions due to L. tropica may develop to ulcerative detectable lesions as discussed by Masoudzadeh et al [30], like the case in our study, so monitoring lesion size could strongly reflect the immune response obtained from the vaccines used.…”

Vaccines for leishmaniasis and the implications of their development for American tegumentary leishmaniasis

“…photosensitization; 65 impairing the mannose activation pathway 66 ) and challenge have indicated promise but have not yet reached advanced phases of clinical development. [67][68][69] Targeted genetic modification to attenuate or delete specific virulence genes within Leishmania is considered a powerful strategy with the potential to provide crossprotective parasites with improved safety profiles, examples are described on Table 1. While the first attempts using attenuated Leishmania parasites rendered protection in murine models, lack of knowledge regarding potential reversion to a wild type genotype left the parasites unsuitable for use in human populations.…”