Immunoliposomes containing Soluble Leishmania Antigens (SLA) as a novel antigen delivery system in murine model of leishmaniasis

Eskandari, Faeze; Talesh, Ghazal Alipour; Parooie, Maryam; Jaafari, Mahmoud Reza; Khamesipour, Ali; Saberi, Zahra; Abbasi, Azam; Badiee, Ali

doi:10.1016/j.exppara.2014.08.016

Cited by 29 publications

(16 citation statements)

References 61 publications

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“…13,14 Several types of micro-or nanoformulations (ie, liposomes, chitosan, PLGA) and antigens have been tested up till now for vaccine development against leishmaniasis with encouraging results. 15,16 In particular, whole heat-inactivated Leishmania major parasites, the causative agent of cutaneous leishmaniasis (CL), or their soluble antigens 17,18 as well as specific parasitic antigens (eg, KMP-11) 19 in combination with adjuvants have been evaluated in experimental models of CL or VL with promising results.…”

Section: Introductionmentioning

confidence: 99%

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Margaroni¹,

Agallou²,

Athanasiou³

et al. 2017

IJN

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Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L. infantum parasites in BALB/c mice. Vaccination with these multifunctionalized PLGA nanoformulations conferred significant protection against parasite infection in vaccinated mice. In particular, vaccination with PLGA-sLiAg-MPLA or p8-PLGA-sLiAg NPs resulted in almost complete elimination of the parasite in the spleen for up to 4 months post-challenge. Parasite burden reduction was accompanied by antigen-specific humoral and cellular immune responses. Specifically, injection with PLGA-sLiAg-MPLA raised exclusively anti-sLiAg IgG1 antibodies post-vaccination, while in p8-PLGA-sLiAg-vaccinated mice, no antibody production was detected. However, 4 months post-challenge, in mice vaccinated with all the multifunctionalized NPs, antibody class switching towards IgG2a subtype was observed. The study of cellular immune responses revealed the increased proliferation capacity of spleen cells against sLiAg, consisting of IFNγ-producing CD4 + and CD8 + T cells. Importantly, the activation of CD8 + T cells was exclusively attributed to vaccination with PLGA NPs surface-modified with the p8 peptide. Moreover, characterization of cytokine production in vaccinated–infected mice revealed that protection was accompanied by significant increase of IFNγ and lower levels of IL-4 and IL-10 in protected mice when compared to control infected group. Conclusively, the above nanoformulations hold promise for future vaccination strategies against VL.

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Section: Introductionmentioning

confidence: 99%

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Margaroni¹,

Agallou²,

Athanasiou³

et al. 2017

IJN

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“…SLA encapsulation in cationic liposomes is ~35% that is in agreement with our previous studies. 15,24 The SLA encapsulation decreased to 27.3% after PEGylation with 7.5% mol, but there was no significant difference between PEGylated formulations and non-PEGylated one.…”

Section: Discussionmentioning

confidence: 93%

PEGylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model

Naseri

Eskandari

Jaafari

et al. 2017

Parasite Immunology

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Although there have been several attempts to develop a vaccine against leishmaniasis, no vaccine in human has been developed yet. Liposomes consisting of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against Leishmania major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study. Liposomal SLA consisting different concentrations of PEG (1.9%-15% mol) were prepared. BALB/c mice were immunized three times in 3 weeks intervals with different formulations. Lesion development and parasite burden in footpad and spleen were evaluated to specify the type of generated immune response and extent of protection. Th1/Th2 cytokine profiles and IgG isotypes were also analysed. The maximum protection was observed in mice immunized with Lip-SLA or pLip-SLA (1.9%) due to smaller footpad swelling, reduction in parasite load, an increase in IgG2a and IFN-γ production. Our results showed that immunization of mice with a high level of PEG (>7.5%) did not improve protective immunity of liposomal SLA. The presence of PEG, particularly more than 3.75%, is not recommended for protection against leishmaniasis.

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“…Improvement of vaccines and treatment strategies is imperative against leishmaniosis. In this context, new adjuvants are required to elicit an intense immune response needed for protection [ 41 ]. In particular, the vaccine adjuvant properties of imiquimod (TLR7a) and resiquimod (TLR7/8a) have been previously studied [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Cytokine Effect of TLR3, TLR4, and TLR7 Agonists Alone or Associated withLeishmania infantumAntigen on Blood from Dogs

Martínez-Orellana

Montserrat‐Sangrà

Quirola-Amores

et al. 2018

BioMed Research International

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Activation of toll-like receptors (TLRs) has been shown to play an important role in leishmaniosis by enhancing the parasite specific immune responses to control infection. However, the role of TLR agonists has not been studied in detail in dogs. The aim of this study was to determine the effect of TLR3, TLR4, and TLR7 agonists (TLR3a, TLR4a, and TLR7a) alone or in combination with Leishmania infantum antigen (LSA) on TNF-α and IL-6 production in blood from dogs living in endemic areas of canine leishmaniosis (CanL). Twenty-four healthy dogs from Catalonia (n=14) and Ibizan hound dogs from the island of Mallorca (n=10) were enrolled. Whole blood with TLR3a, TLR4a, and TLR7a alone or combined with LSA were cultured separately, and IFN-γ, TNF-α, and IL-6 were measured by ELISA. A significant increase of TNF-α was found for all conditions studied compared to medium alone. Stimulation with TLR4a (p=0.0001) and TLR7a (p=0.005) presented a significantly marked increase in TNF-α and IL-6 production compared to TLR3a. Importantly, significantly higher TNF-α production was found in LSA+TLR4a (p=0.0001) stimulated blood and LSA+TLR7a (p=0.005) compared to LSA alone. All dogs showed higher TNF-α production after LSA+TLR7a compared to TLR7a (p=0.047) and LSA+TLR3a compared to TLR3a (p=0.052). These data indicate a marked inflammatory cytokine effect of TLR4a and TLR7a on blood from healthy dogs living in endemic areas of CanL. Additionally, LSA+TLR7a promoted a synergistic proinflammatory effect with TNF-α in all dogs. Those findings suggest an active role of TLRs in proinflammatory responses, which might be strongly involved in the process of disease resolution.

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Immunoliposomes containing Soluble Leishmania Antigens (SLA) as a novel antigen delivery system in murine model of leishmaniasis

Cited by 29 publications

References 61 publications

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

PEGylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model

Cytokine Effect of TLR3, TLR4, and TLR7 Agonists Alone or Associated withLeishmania infantumAntigen on Blood from Dogs

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Immunoliposomes containing Soluble Leishmania Antigens (SLA) as a novel antigen delivery system in murine model of leishmaniasis

Cited by 29 publications

References 61 publications

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNF&alpha;-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNF&alpha;-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

PEGylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model

Cytokine Effect of TLR3, TLR4, and TLR7 Agonists Alone or Associated withLeishmania infantumAntigen on Blood from Dogs

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Product

Resources

About

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble <em>Leishmania</em> antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis