Evaluation of different total Leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a Toll-like receptor-3 agonist to prevent cutaneous leishmaniasis

Germanó, María José; Lozano, Esteban; Sánchez, María Victoria; Bruna, Flavia; Bustos, María Fernanda García; Lochedino, Arianna Lourdes Sosa; Salomón, María Cristina; Fernandes, Ana Paula; Mackern-Oberti, Juan Pablo; Cargnelutti, Diego Esteban

doi:10.1590/0074-02760200067

Cited by 5 publications

(7 citation statements)

References 32 publications

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“…Recently, it was demonstrated that antigen similar to LaAg associated to poly I:C induced partial protection in BALB/c mice, and without adjuvant enhanced the lesion size and parasite load, as expected [46]. Poly I:C is a TLR3 ligand and a possible candidate in vaccine formulation against Leishmania spp.…”

Section: Discussionsupporting

confidence: 57%

MPLA and AddaVax® Adjuvants Fail to Promote Intramuscular LaAg Vaccine Protectiveness against Experimental Cutaneous Leishmaniasis

et al. 2021

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There is so far no vaccine approved for human leishmaniasis, mainly because of the lack of appropriate adjuvants. This study aimed to evaluate in mice the capacity of a mixture of monophosphoryl lipid A (MPLA) and AddaVax® adjuvants in enhancing the efficacy of a Leishvacin®-like vaccine comprised of Leishmania amazonensis whole antigens (LaAg). For that, mice were immunized with LaAg plus MPLA/AddaVax® by the intramuscular route (i.m.) prior to challenge with 2 × 105 and 2 × 106 living parasites. Immunization with LaAg alone reduced the lesion growth of the 2 × 105-challenged mice only in the peak of infection, but that was not accompanied by reduced parasite load, and thus not considered protective. Mice given a 2 × 106 -challenge were not protected by LaAg. The association of LaAg with MPLA/AddaVax® was able to enhance the cutaneous hypersensitivity response compared with LaAg alone. Despite this, there was no difference in proliferative cell response to antigen ex vivo. Moreover, regardless of the parasite challenge, association of LaAg with MPL/AddaVax® did not significantly enhance protection in comparison with LaAg alone. This work demonstrated that MPL/AddaVax® is not effective in improving the efficacy of i.m. LaAg vaccine against cutaneous leishmaniasis.

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Section: Discussionsupporting

confidence: 57%

MPLA and AddaVax® Adjuvants Fail to Promote Intramuscular LaAg Vaccine Protectiveness against Experimental Cutaneous Leishmaniasis

et al. 2021

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“…The humoral immune response induced by the experimental treatment was evaluated by measuring total specific IgG, IgG1 and IgG2a by enzyme linked immunosorbent assay (ELISA) in serum samples collected on week 3 and 10 of the protocol. 11 …”

Section: Methodsmentioning

confidence: 99%

Therapeutic effect of Prosopis strombulifera (LAM) BENTH aqueous extract on a murine model of cutaneous leishmaniasis

Lozano

Germanó

Troncoso

et al. 2022

Journal of Traditional and Complementary Medicine

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“…Twenty-one days after each immunization, blood samples were obtained from twice-immunized mice. Anti-TLA IgG antibodies were determined 21 days after prime and boost, while anti-TLA IgG1 and IgG2a isotypes were determined 21 days after boost by enzyme-linked immunosorbent assay ( 16 ). Thus, 96-well plates were incubated with 3 μg/well of TLA overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, it has been demonstrated that Poly (I:C) can induce the cross-presentation of antigens by DC and, consequently, enhance the CD8+ T-cell response, which is important to control intracellular parasitic infection ( 15 ). Our research group has previously demonstrated that total L. amazonensis antigens (TLAs), obtained by cycles of freezing and thawing or sonication, combined with Poly (I:C) as adjuvant, were able to partially protect BALB/c mice against the L. amazonensis infection ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Immunodominant Antigens From a First-Generation Vaccine Against Cutaneous Leishmaniasis

et al. 2022

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Leishmaniasis is a neglected tropical disease (NTD) caused by parasites belonging to the Leishmania genus for which there is no vaccine available for human use. Thus, the aims of this study are to evaluate the immunoprotective effect of a first-generation vaccine against L. amazonensis and to identify its immunodominant antigens. BALB/c mice were inoculated with phosphate buffer sodium (PBS), total L. amazonensis antigens (TLAs), or TLA with Poly (I:C) and Montanide ISA 763. The humoral and cellular immune response was evaluated before infection. IgG, IgG1, and IgG2a were measured on serum, and IFN-γ, IL-4, and IL-10 cytokines as well as cell proliferation were measured on a splenocyte culture from vaccinated mice. Immunized mice were challenged with 104 infective parasites of L. amazonensis on the footpad. After infection, the protection provided by the vaccine was analyzed by measuring lesion size, splenic index, and parasite load on the footpad and spleen. To identify immunodominant antigens, total proteins of L. amazonensis were separated on 2D electrophoresis gel and transferred to a membrane that was incubated with serum from immunoprotected mice. The antigens recognized by the serum were analyzed through a mass spectrometric assay (LC-MS/MS-IT-TOF) to identify their protein sequence, which was subjected to bioinformatic analysis. The first-generation vaccine induced higher levels of antibodies, cytokines, and cell proliferation than the controls after the second dose. Mice vaccinated with TLA + Poly (I:C) + Montanide ISA 763 showed less footpad swelling, a lower splenic index, and a lower parasite load than the control groups (PBS and TLA). Four immunodominant proteins were identified by mass spectrometry: cytosolic tryparedoxin peroxidase, an uncharacterized protein, a kinetoplast-associated protein-like protein, and a putative heat-shock protein DNAJ. The identified proteins showed high levels of conserved sequence among species belonging to the Leishmania genus and the Trypanosomatidae family. These proteins also proved to be phylogenetically divergent to human and canine proteins. TLA + Poly (I:C) + Montanide ISA 763 could be used as a first-generation vaccine against leishmaniasis. The four proteins identified from the whole-protein vaccine could be good antigen candidates to develop a new-generation vaccine against leishmaniasis.

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Evaluation of different total Leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a Toll-like receptor-3 agonist to prevent cutaneous leishmaniasis

Cited by 5 publications

References 32 publications

MPLA and AddaVax® Adjuvants Fail to Promote Intramuscular LaAg Vaccine Protectiveness against Experimental Cutaneous Leishmaniasis

MPLA and AddaVax® Adjuvants Fail to Promote Intramuscular LaAg Vaccine Protectiveness against Experimental Cutaneous Leishmaniasis

Therapeutic effect of Prosopis strombulifera (LAM) BENTH aqueous extract on a murine model of cutaneous leishmaniasis

Identification of Immunodominant Antigens From a First-Generation Vaccine Against Cutaneous Leishmaniasis

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