A vaccine composed of a hypothetical protein and the eukaryotic initiation factor 5a from Leishmania braziliensis cross-protection against Leishmania amazonensis infection

Duarte, Mariana C.; Lage, Daniela P.; Martins, Vívian T.; Costa, Lourena E.; Carvalho, Ana Maria Ravena Severino; Ludolf, Fernanda; Santos, Thaís Teodoro de Oliveira; Vale, Danniele L.; Roatt, Bruno Mendes; Menezes‐Souza, Daniel; Fernandes, Ana Paula; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antônio Ferraz

doi:10.1016/j.imbio.2016.09.015

Cited by 17 publications

(18 citation statements)

References 58 publications

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“…Eight-week-old female BALB/c mice were obtained from the breeding facilities of the Department of Biochemistry and Immunology, Institute of Biological Sciences, UFMG (Brazil) and were maintained under specific-pathogen-free conditions. L. amazonensis (IFLA/BR/1967/PH-8) was cultured as previously described [33]. The soluble L. amazonensis antigen (SLA) was prepared from stationary-phase promastigotes as described elsewhere [34].…”

Section: Mice Parasites and Preparation Of Soluble Agmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis.

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Section: Mice Parasites and Preparation Of Soluble Agmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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“…In agreement with the results obtained in this work, the incapacity to control IL-4 or IL-10 production beside the induction of IFN-γ was considered as a bad marker for protection (Roberts et al, 2005 ) as it has been correlated with the inability to generate protective responses in BALB/c mice against L. major (Sjölander et al, 1998 ; Iborra et al, 2005 , 2007 ) or L. infantum (Pirdel et al, 2014 ). The failure in protection showed in this work for the BALB/c CL model may be related to the necessity to control the responses mediated by IL-4 and by IL-10 besides generating IFN-γ as occurred with other tested vaccines against the parasite in CL (Gomes et al, 2012 ; Soto et al, 2015 ; Duarte et al, 2017 ) or VL models (Goto et al, 2011 ; Martins et al, 2017 ). On the other hand, protection in the C57BL/6- L. major model was associated to the induction of rapid IFN-γ mediated responses after infective challenge rather than the control of Th2 or IL-10 mediated responses as occurred with different vaccines based on parasite antigens or Leishmania live vaccines (Iborra et al, 2005 ; Kébaïer et al, 2006 ; Doroud et al, 2011 ; Peters et al, 2012 ; Solana et al, 2017 ).…”

Section: Discussionmentioning

confidence: 78%

“…Importantly, experimental vaccines based on the PABPs (Soto et al, 2015 ) or LeIF4A, either alone (Skeiky et al, 1998 ) or fused with other parasite antigens forming a recombinant poly-protein (Coler et al, 2002 , 2007 ; Bertholet et al, 2009 ), have the potential of inducing protection against the infection with different Leishmania species. Similarly, a recombinant version of the LbeIF5a factor was able to induce protection against L. infantum (Duarte et al, 2016a ) and Leishmania amazonensis (Duarte et al, 2017 ) challenges when administered as part of a polyprotein vaccine.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis

Garde

Ramírez

Corvo

et al. 2018

Front. Cell. Infect. Microbiol.

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Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania. Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, β, and γ subunits and the α, β, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2) or F2B (LieIF2B), respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum. In L. infantum (BALB/c) and Leishmania major (BALB/c or C57BL/6) challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bβ and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the production of the down-regulatory IL-10 cytokine, favoring a pathological outcome. Therefore, these proteins might be considered markers of disease.

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“…For TL, protection against infection is associated with the development of a parasite-specific Th1 immunity, based on the production of cytokines, such as IFN- γ , IL-2, IL-12 and GM-CSF. In contrast, IL-4, IL-10, IL-13 and transforming growth factor- β (TGF- β ), among other anti-inflammatory molecules are associated with susceptibility to the infection in the mammalian hosts (Coelho et al ., 2003; Costa et al ., 2015; Duarte et al ., 2017).…”

Section: Discussionmentioning

confidence: 99%

High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection

et al. 2018

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In the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.

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A vaccine composed of a hypothetical protein and the eukaryotic initiation factor 5a from Leishmania braziliensis cross-protection against Leishmania amazonensis infection

Cited by 17 publications

References 58 publications

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis

High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection

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