Publications by authors named "Sima Habibzadeh"

13 Publications

  • Page 1 of 1

Evaluation of protection induced by in vitro maturated BMDCs presenting CD8 T cell stimulating peptides after a heterologous vaccination regimen in BALB/c model against Leishmania major.

Exp Parasitol 2021 Apr 11;223:108082. Epub 2021 Feb 11.

Immunotherapy and Leishmania Vaccine Research Department, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Leishmaniasis is a complex vector-borne disease mediated by Leishmania parasite and a strong and long-lasting CD4 Th1 and CD8-T cell immunity is required to control the infection. Thus far multivalent subunit vaccines have met this requirement more promisingly. However several full protein sequences cannot be easily arranged in one construct. Instead, new emerging immune-informatics based epitope formulations surpass this restriction. Herein, we aimed to examine the protective potential of a dendritic cell based vaccine presenting epitopes to CD8 and CD4-T cells in combination with DNA vaccine encoding the same epitopes against murine cutaneous leishmaniasis. Immature DCs were loaded with epitopes (selected from parasite proteome) in vitro with or without CpG oligonucleotides and were used to immunize BALB/c mice. Peptide coding DNA was used to boost the system and immunological responses were evaluated after Leishmania (L.) major infectious challenge. The pre-challenge response to included epitopes was Th1 polarized which potentially lowered the infection at early time points post-challenge but not at later weeks. Collectively, DC prime-DNA boost was found to be a promising approach for Th1 polarization however the constituent epitopes undoubtedly make a significant contribution in the protection outcome of the vaccine.
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http://dx.doi.org/10.1016/j.exppara.2021.108082DOI Listing
April 2021

Corrigendum to "Antileishmanial effect of rapamycin as an alternative approach to control Leishmania tropica infection" [Vet. Parasitol. 276 (2019) 108976].

Vet Parasitol 2021 Mar 10;291:109305. Epub 2020 Dec 10.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.vetpar.2020.109305DOI Listing
March 2021

Role of polymorphisms of the endothelial nitric oxide synthase gene in predicting slow-flow phenomenon after primary percutaneous coronary intervention.

Turk Kardiyol Dern Ars 2020 07;48(5):472-483

Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Objective: The aim of the present study was to examine the association between 2 polymorphisms of the endothelial nitric oxide (eNOS) gene (-786T>C and +894G>T) and the no-reflow/slow-flow phenomenon in post-primary percutaneous coronary intervention (PPCI) patients.

Methods: A total of 103 post-PPCI patients were enrolled. Coronary no-reflow phenomenon was defined as a Thrombolysis in Myocardial Infarction (TIMI) flow grade 0-1 and coronary slow-flow phenomenon (CSFP) was defined as a TIMI flow grade ≤2.

Results: Due to the small number of post-PPCI patients with the no-reflow phenomenon (n=4), the primary comparison was made between CSFP (n=20) and normal flow (n=83) groups. There was a greater frequency of CSFP among carriers of the -786C allele of the eNOS -786T>C polymorphism (odds ratio [OR]: 3.90; 95% confidence interval [CI]: 0.87-17.45; p=0.07). However, no such association was detected between the +894T allele of the eNOS +894G>T and CSFP (OR: 0.92; 95% CI: 0.21-3.98; p=0.91). In the adjusted analysis, the -786T>C polymorphism did not reach statistical significance.

Conclusion: There was no significant association between CSFP and 2 of the most common polymorphisms of the eNOS gene in post-PPCI patients.
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http://dx.doi.org/10.5543/tkda.2020.53849DOI Listing
July 2020

Visualization of Leishmania tropica Infection in BALB/c Mice by Bioluminescence Imaging

Iran Biomed J 2020 05 1;24(3):164-72. Epub 2019 Dec 1.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Background: Leishmania tropica is the cause of more than one form of leishmaniasis and lacks a known reservoir animal. This study compares the potential infectivity of recombinant and wild-type L. tropica in BALB/c mice.

Methods: The potential infectivity of recombinant L. tropicaEGFP or L. tropicaEGFP-LUC by two different, the subcutaneous and intradermal, routes was compared using a range of classical detection methods and bioluminescence imaging (BLI).

Results: In addition to the results obtained from classical diagnostic approaches, the BLI signals were detected in footpads and ears of L. tropica-infected animals. The BLI revealed that a bioluminescence signal can be observed at the inoculation site. The stability of the BLI remained constant in the footpad, but the signal was detectable for only three months in the pinna due to the decline in infection over time.

Conclusion: The presented data are a precise verification of the assumption that BALB/c mice could be used as an experimental model for L. tropica infectivity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275622PMC
May 2020

The outcome of arginase activity inhibition in BALB/c mice hosting Leishmania tropica.

Parasite Immunol 2020 03 7;42(3):e12691. Epub 2020 Jan 7.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Two species of Leishmania (L), L. tropica and L. major, are among the main causative agents of cutaneous leishmaniasis. Arginase (ARG) is an essential enzyme for cell growth, thus an attractive drug target. In this study, we tried to survey the inhibitory impact of ARG by nor-NOHA (N-ω-hydroxy-L-nor-arginine) on in vivo infection caused by L. tropica. BALB/c mice were inoculated with L. tropica (Ltrop) or L. major (Lmj) and then were treated by nor-NOHA. ARG inhibitor only indicated a delay in generation of a cutaneous lesion in inoculated footpad with nor-NOHA-Ltrop and nor-NOHA-Lmj. ARG activity has been significantly reduced in nor-NOHA-Ltrop group. In this group, ARG activity inhibition correlated with increased levels of nitric oxide (NO). In both inoculated mice with Ltrop or Lmj, parasite load showed a significant decrease at later steps during the CL course post-treatment. In vivo bioluminescence intensity did not show any ARG's inhibitory effect on treated-Ltrop. The findings verified that the ARG activity may partially control the L. tropica infection in BALB/c mice through reduction of parasite proliferation and parasite killing through NO generation. This effect is dose-dependent.
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http://dx.doi.org/10.1111/pim.12691DOI Listing
March 2020

Antileishmanial effect of rapamycin as an alternative approach to control Leishmania tropica infection.

Vet Parasitol 2019 Dec 10;276:108976. Epub 2019 Nov 10.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Cutaneous leishmaniosis (CL) is a parasitic disease in animals and human with no satisfactory treatments and vaccination. Rapamycin is a potent inhibitor of mammalian target of rapamycin (mTOR) with various applications. Here, the effect of rapamycin alone or in combination with two other drugs, namely amphotericin B (AmB) and glucantime, was investigated against Leishmania tropica infection. In vitro viability and electron microscopy evaluation of the parasites showed detrimental changes in their appearance and viability. Treatment with clinically relevant dose of rapamycin (10.2 μg/dose) is able to control the parasite load in BALB/c mice infected with L. tropica. Furthermore, the cytokine profiles showed significant polarization towards Th1 immune response. Surprisingly, combination therapy with either AmB or glucantime was not efficient. Rapamycin is showed an effective alternative therapy against leishmaniosis caused by L. tropica.
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http://dx.doi.org/10.1016/j.vetpar.2019.108976DOI Listing
December 2019

DNA plasmid coding for Phlebotomus sergenti salivary protein PsSP9, a member of the SP15 family of proteins, protects against Leishmania tropica.

PLoS Negl Trop Dis 2019 01 11;13(1):e0007067. Epub 2019 Jan 11.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Background: The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies, which transmits Leishmania parasites together with saliva during blood feeding. In Iran, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) major and L. tropica, and their main vectors are Phlebotomus (Ph.) papatasi and Ph. sergenti, respectively. Previous studies have demonstrated that mice immunized with the salivary gland homogenate (SGH) of Ph. papatasi or subjected to bites from uninfected sand flies are protected against L. major infection.

Methods And Results: In this work we tested the immune response in BALB/c mice to 14 different plasmids coding for the most abundant salivary proteins of Ph. sergenti. The plasmid coding for the salivary protein PsSP9 induced a DTH response in the presence of a significant increase of IFN-γ expression in draining lymph nodes (dLN) as compared to control plasmid and no detectable PsSP9 antibody response. Animals immunized with whole Ph. sergenti SGH developed only a saliva-specific antibody response and no DTH response. Mice immunized with whole Ph. sergenti saliva and challenged intradermally with L. tropica plus Ph. sergenti SGH in their ears, exhibited no protective effect. In contrast, PsSP9-immunized mice showed protection against L. tropica infection resulting in a reduction in nodule size, disease burden and parasite burden compared to controls. Two months post infection, protection was associated with a significant increase in the ratio of IFN-γ to IL-5 expression in the dLN compared to controls.

Conclusion: This study demonstrates that while immunity to the whole Ph. sergenti saliva does not induce a protective response against cutaneous leishmaniasis in BALB/c mice, PsSP9, a member of the PpSP15 family of Ph. sergenti salivary proteins, provides protection against L. tropica infection. These results suggest that this family of proteins in Ph. sergenti, Ph. duboscqi and Ph. papatasi may have similar immunogenic and protective properties against different Leishmania species. Indeed, this anti-saliva immunity may act as an adjuvant to accelerate the cell-mediated immune response to co-administered Leishmania antigens, or even cause the activation of infected macrophages to remove parasites more efficiently. These findings highlight the idea of applying arthropod saliva components in vaccination approaches for diseases caused by vector-borne pathogens.
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http://dx.doi.org/10.1371/journal.pntd.0007067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345478PMC
January 2019

Live Leishmania tarentolae secreting HNP1 as an immunotherapeutic tool against Leishmania infection in BALB/c mice.

Immunotherapy 2017 10;9(13):1089-1102

Department of Immunotherapy & Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran, 13194.

Aim: Several disadvantages about chemotherapy for leishmaniasis has reinforced discovery of novel therapeutic agents especially immunotherapeutics. HNP1, as a member of the mammalian antimicrobial peptides family, is an attractive molecule due to its broad functional spectrum. Here, the in vivo potency of HNP1 in transgenic Leishmania tarentolae as an immunotherapy tool against Leishmania major-infected BALB/c mice was examined.

Methods & Results: 3 weeks after infection with L. major, the treatment effect of L. tarentolae-HNP1-EGFP was pursued. The results were promising in respect to parasite load control and Th1 immune response polarization compared with controls.

Conclusion: Immunotherapy by live L. tarentolae secreting HNP1 can elicit cellular immune response in a susceptible mouse model in order to control L. major infection.
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http://dx.doi.org/10.2217/imt-2017-0076DOI Listing
October 2017

A novel non-invasive diagnostic sampling technique for cutaneous leishmaniasis.

PLoS Negl Trop Dis 2017 Jul 13;11(7):e0005750. Epub 2017 Jul 13.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Accurate diagnosis of cutaneous leishmaniasis (CL) is important for chemotherapy and epidemiological studies. Common approaches for Leishmania detection involve the invasive collection of specimens for direct identification of amastigotes by microscopy and the culturing of promastigotes from infected tissues. Although these techniques are highly specific, they require highly skilled health workers and have the inherent risks of all invasive procedures, such as pain and risk of bacterial and fungal super-infection. Therefore, it is essential to reduce discomfort, potential infection and scarring caused by invasive diagnostic approaches especially for children. In this report, we present a novel non-invasive method, that is painless, rapid and user-friendly, using sequential tape strips for sampling and isolation of DNA from the surface of active and healed skin lesions of CL patients. A total of 119 patients suspected of suffering from cutaneous leishmaniasis with different clinical manifestations were recruited and samples were collected both from their lesions and from uninfected areas. In addition, 15 fungal-infected lesions and 54 areas of healthy skin were examined. The duration of sampling is short (less than one minute) and species identification by PCR is highly specific and sensitive. The sequential tape stripping sampling method is a sensitive, non-invasive and cost-effective alternative to traditional diagnostic assays and it is suitable for field studies as well as for use in health care centers.
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http://dx.doi.org/10.1371/journal.pntd.0005750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526608PMC
July 2017

Antitumor Effect of IP-10 by Using Two Different Approaches: Live Delivery System and Gene Therapy.

J Breast Cancer 2016 Mar 25;19(1):34-44. Epub 2016 Mar 25.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Purpose: Immunotherapy is one of the treatment strategies for breast cancer, the most common cancer in women worldwide. In this approach, the patient's immune system is stimulated to attack microscopic tumors and control metastasis. Here, we used interferon γ-induced protein 10 (IP-10), which induces and strengthens antitumor immunity, as an immunotherapeutic agent. We employed Leishmania tarentolae, a nonpathogenic lizard parasite that lacks the ability to persist in mammalian macrophages, was used as a live delivery system for carrying the immunotherapeutic agent. It has been already shown that arginase activity, and consequently, polyamine production, are associated with tumor progression.

Methods: A live delivery system was constructed by stable transfection of pLEXSY plasmid containing the IP-10-enhanced green fluorescent protein (IP-10-egfp) fusion gene into L. tarentolae. Then, the presence of the IP-10-egfp gene and the accurate integration location into the parasite genome were confirmed. The therapeutic efficacy of IP-10 delivered via L. tarentolae and recombinant pcDNA-(IP-10-egfp) plasmid was compared by determining the arginase activity in a mouse 4T1 breast cancer model.

Results: The pcDNA-(IP-10-egfp) group showed a significant reduction in tumor weight and growth. Histological evaluation also revealed that only this group demonstrated inhibition of metastasis to the lung tissue. The arginase activity in the tissue of the pcDNA-(IP-10-egfp) mice significantly decreased in comparison with that in normal mice. No significant difference was observed in arginase activity in the sera of mice receiving other therapeutic strategies.

Conclusion: Our data indicates that IP-10 immunotherapy is a promising strategy for breast cancer treatment, as shown in the 4T1-implanted BALB/c mouse model. However, the L. tarentolae-(IP-10-EGFP) live delivery system requires dose modifications to achieve efficacy in the applied regimen (six injections in 3 weeks). Our results indicate that the arginase assay could be a good biomarker to differentiate tumoral tissues from the normal ones.
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http://dx.doi.org/10.4048/jbc.2016.19.1.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822105PMC
March 2016

Solid lipid nanoparticle loaded with paromomycin: in vivo efficacy against Leishmania tropica infection in BALB/c mice model.

Appl Microbiol Biotechnol 2016 Aug 10;100(16):7051-60. Epub 2016 Mar 10.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Leishmaniasis is a parasitic disease transmitted through the bite of an infected phlebotomine sand fly and caused by protozoan parasites of the genus Leishmania. There is no available vaccine for leishmaniasis in human, and the current chemotherapy approaches are hampered by different clinical problems. Most of available drugs are confined to a limited number of toxic chemical compounds, which some parasite strains have evolved drug resistance against. Hence, drug discovery and production of a new anti leishmanial compound is essential. One promising strategy is using the nanoparticle delivery systems with the aim of accelerating the efficacy of the available treatments. In the present study, paromomycin sulfate (PM) was formulated in solid lipid nanoparticles (SLN) and the in vivo efficacy was investigated against Leishmania tropica in BALB/c mice model. To do so, the increase in footpad thickness was measured and real-time PCR was performed to quantify the parasite load after infectious challenge. The level of nitric oxide and cytokines including interleukin-4 (IL-4) and gamma interferon (IFN -γ) were assessed. Altogether, the results show that PM loaded into SLN is significantly more effective than PM alone in inhibiting the parasite propagation and switching towards Th1 response.
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http://dx.doi.org/10.1007/s00253-016-7422-yDOI Listing
August 2016

EGFP reporter protein: its immunogenicity in Leishmania-infected BALB/c mice.

Appl Microbiol Biotechnol 2016 May 19;100(9):3923-34. Epub 2015 Dec 19.

Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.

Optical reporter genes such as green fluorescent protein (GFP) and luciferase are efficiently and widely used in monitoring and studying the protective/therapeutic potential of candidate agents in leishmaniasis. But several observations and controversial reports have generated a main concern, whether enhanced GFP (EGFP) affects immune response. To address this issue, we studied the immunogenicity of EGFP in vivo by two lines of stably transfected parasites (Leishmania major (EGFP) or L. major (EGFP-LUC)) in BALB/c model and/or as a recombinant protein (rEGFP) produced in vitro by bacteria in parallel. Disease progression was followed by footpad swelling measurements and parasite burden in draining lymph nodes using microtitration assay and real-time PCR, and immune responses were also evaluated in spleen. EGFP-expressing parasites generated larger swellings in comparison with wild-type (L. major) while mice immunized with rEGFP and challenged with wild-type parasite were quite comparable in footpad swelling with control group without significant difference. However, both conventional and molecular approaches revealed no significant difference in parasite load between different groups. More importantly, no significant inflammatory responses were detected in groups with higher swelling size measured by interferon-γ (IFN-γ), interleukin (IL)-10, IL-5, and nitric oxide against frozen and thawed lysate of parasite as stimulator. Altogether, these results clearly revealed that EGFP protein expressed in prokaryotic and eukaryotic hosts is not an immunological reactive molecule and acts as a neutral protein without any side effects in mice. So, EGFP expressing Leishmania could be a safe and reliable substitution for wild-types that simplifies in situ follow-up and eliminates the animal scarification wherever needed during the study.
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http://dx.doi.org/10.1007/s00253-015-7201-1DOI Listing
May 2016