scholarly journals The Leishmania infantum Acidic Ribosomal Protein P0 Administered as a DNA Vaccine Confers Protective Immunity to Leishmania major Infection in BALB/c Mice

2003 ◽  
Vol 71 (11) ◽  
pp. 6562-6572 ◽  
Author(s):  
Salvador Iborra ◽  
Manuel Soto ◽  
Javier Carrión ◽  
Ana Nieto ◽  
Edgar Fernández ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Leishmania Infantum ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Immunological Response ◽  
Humoral Response ◽  
Ifn Γ ◽  
Immunogenic Properties ◽  
Ribosomal Protein P0 ◽  
Acidic Ribosomal Protein

ABSTRACT In this study, we examined the immunogenic properties of the Leishmania infantum acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and cellular responses induced by the administration of the LiP0 antigen, either as soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0), were determined. Also, the immunological response associated with a prime-boost strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like humoral response, but no anti-LiP0 antibodies were induced after immunization with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized with the prime-boost regime. For all three immunization protocols, rLiP0-stimulated production of gamma interferon (IFN-γ) in both splenocytes and lymph node cells from immunized mice was observed. However, it was only when mice were immunized with pcDNA3-LiP0 that noticeable protection against L. major infection was achieved, as determined by both lesion development and parasite burden. Immunization of mice with LiP0-DNA primes both CD4+ and CD8+ T cells, which, with the L. major challenge, were boosted to produce significant levels of IL-12-dependent, antigen-specific IFN-γ. Taken together, these data indicate that genetic vaccination with LiP0 induces protective immunological effector mechanisms, yet the immunological response elicited by LiP0 is not sufficient to keep the infection from progressing.

scholarly journals Subcutaneous immunization against Leishmania major - infection in mice: efficacy of formalin-killed promastigotes combined with adjuvants

2010 ◽  
Vol 52 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Joshua M. Mutiso ◽  
John C. Macharia ◽  
Rosemary M. Mutisya ◽  
Evans Taracha
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Immune Status ◽  
Parasite Burden ◽  
Interferon Γ ◽  
Cutaneous Lesions ◽  
Ifn Γ ◽  
Efficacious Vaccine ◽  
Subcutaneous Immunization ◽  
Murine Cutaneous Leishmaniasis

Formalin-killed promastigotes (FKP) of Leishmania major, in combination with Montanide ISA 720 (MISA), BCG or alum were used in vaccination of an inbred murine model against cutaneous leishmaniasis (CL). Significant and specific increases in anti-FKP IgG responses were detected for both alum-FKP and BCG-FKP compared to MISA-FKP (p < 0.001). Significant increases in splenic lymphocyte recall proliferation was obtained in the MISA-FKP vaccinated mice compared to alum-FKP or BCG-FKP vaccinated groups (p < 0.01). The highest interferon-γ responses were observed in the BCG-FKP group followed by the MISA-FKP while the alum-FKP gave the least responses. Significantly reduced lesion sizes were obtained in the MISA-FKP group compared to the BCG/alum adjuvants-FKP vaccinated groups. Although the BCG-FKP group showed the highest IFN-γ responses, it failed to control cutaneous lesions. Significant reductions in parasite numbers were observed in the MISA-FKP and BCG-FKP vaccinated groups (p < 0.001). There was a good correlation between parasite burden and IFN-γ level indicating IFN-γ response as a sensitive parameter of the immune status. In conclusion, MISA-FKP is the most efficacious vaccine formulation against murine cutaneous leishmaniasis.

scholarly journals Evaluation of Immune Response against Leishmaniasis in BALB/c Mice Immunized with Cationic DOTAP/DOPE/CHOL Liposomes Containing Soluble Leishmania major Antigens

2019 ◽  
Author(s):  
Mansure HOJATIZADE ◽  
Ali BADIEE ◽  
Ali KHAMESIPOUR ◽  
Mahmoud Reza JAAFARI
Keyword(s):  
Immune Response ◽  
Leishmania Major ◽  
High Titer ◽  
Parasite Burden ◽  
Phase Iii ◽  
Th2 Response ◽  
Liposomal Form ◽  
Lipid Film ◽  
Phase Iii Clinical Trials ◽  
Ifn Γ

Background: Whole killed Leishmania vaccine reached phase III clinical trials but failed to display significant efficacy in human mainly due to limited Th1 inducer adjuvant. Liposomes consisting of 1, 2-dioleoyl-3trimethylammonium-propane (DOTAP) bearing an inherent adjuvanticity and 1, 2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) is well known to intensify the efficacy of positively charged liposomes. Methods: Soluble Leishmania major antigens (SLA) encapsulated in cationic liposomes using lipid film method in 2016). BALB/c mice were immunized subcutaneously (SC), three times in a 2-wk interval, with Lip (DOTAP)-SLA+, Lip (DOTAP/DOPE)-SLA+, Lip (DOTAP/DOPE/CHO)-SLA+, Lip (DOTAP/DOPE/CHO), Lip (DOPE/CHO), SLA or HEPES buffer. At week 2 after the last booster injection, immunized mice have challenged SC in the footpad with L. major parasites. To investigate the rate of protection and the type of immune response generated in mice, lesions development was assessed, IL-4 and IFN-γ levels with the ratio of IgG2a/IgG1 isotype were studied to describe the type of generated immune response. Results: Mice immunized with all liposomal form of SLA showed smaller footpad swelling and lower parasite burden in the spleen and footpad compared to the group of mice received buffer. However, these formulations did not show protection against leishmaniosis because of a generated mixed Th1/Th2 response in mice characterized by high production of IFN-γ and IL4 and a high titer of IgG1 and IgG2a antibody. Conclusion: Immunization with Lip (DOTAP/DOPE/CHO)-SLA+ was not an appropriate strategy to protect mice against leishmaniosis.

scholarly journals Vaccination with the Leishmania infantum Acidic Ribosomal P0 Protein plus CpG Oligodeoxynucleotides Induces Protection against Cutaneous Leishmaniasis in C57BL/6 Mice but Does Not Prevent Progressive Disease in BALB/c Mice

2005 ◽  
Vol 73 (9) ◽  
pp. 5842-5852 ◽  
Author(s):  
Salvador Iborra ◽  
Javier Carrión ◽  
Charles Anderson ◽  
Carlos Alonso ◽  
David Sacks ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Infantum ◽  
Progressive Disease ◽  
Immunological Response ◽  
Parasite Load ◽  
Th2 Response ◽  
Suitable Alternative ◽  
Cpg Oligodeoxynucleotides ◽  
Potential Efficacy ◽  
Ifn Γ

ABSTRACT We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on the Leishmania infantum acidic ribosomal protein P0 (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L. major parasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces the L. major infection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-γ) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-γ in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced by L. major infection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.

scholarly journals 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

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad Maarouf ◽  
Alyaa A. Abdlwahab
Keyword(s):  
Lymph Nodes ◽  
Ribosomal Protein ◽  
Dna Vaccine ◽  
Parasite Burden ◽  
Leishmania Tropica ◽  
Ifn Γ ◽  
Ribosomal Protein L5 ◽  
Protective Strategies ◽  
Efficacious Vaccine ◽  
Draining Lymph Nodes

Cutaneous leishmaniasis in Syria is caused mainly by Leishmania tropica. It represents a serious health problem, which has aggravated further after the civil war in the country. Until now, there are no effective protective strategies, safe therapy, or efficacious vaccine to protect from this infection. DNA vaccines represent a promising approach for achieving protection against leishmaniasis. The L5 ribosomal protein plays fundamental roles in the assembly process of the ribosome subunits, so this study has chosen the ribosomal protein L5 gene to design a DNA vaccine against Leishmania tropica infection. After proving the existence of the ribosomal protein L5 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), it was sequenced and cloned into a pCI plasmid, and the designed DNA vaccine was administered to BALB/c mice. The protective response was evaluated by measuring lesion development in immunized BALB/c mice for 6 weeks after challenging mice with the parasite. RT-qPCR was used to quantify IL-12, IFN-γ, and IL-4 in draining lymph nodes (DLNs) of immunized mice. In the final week, the parasite burden was determined in footpad lesions and local draining lymph nodes (DLNs). This study demonstrated the presence and expression of the ribosomal protein L5 gene in the Syrian strain of Leishmania tropica promastigotes. The sequence of the ribosomal protein cDNA L5 gene was determined and published in Genbank. The gene size was 918 bp. Expression was also demonstrated at the level of cDNA. This study also demonstrated that vaccination with the ribosomal protein L5 gene induces TH1 response in immunized mice. This response prevents the partial development of a skin lesion of Leishmania.

scholarly journals Parasite load, iNOS and cytokine profiles, and histopathological aspects of Leishmania infantum infection in dogs with different clinical presentations

2019 ◽  
Vol 49 (10) ◽  
Author(s):  
Tassia Cristina Bello de Vasconcelos ◽  
Sávio Freire Bruno ◽  
Luisa Helena Monteiro de Miranda ◽  
Fátima Conceição-Silva ◽  
Vinícius Silva Belo ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Clinical Symptoms ◽  
Immunological Response ◽  
Parasite Load ◽  
Hepatic Tissue ◽  
Inos Mrna ◽  
White Pulp ◽  
Clinical Presentations ◽  
Ifn Γ

ABSTRACT: Visceral leishmaniasis (VL) is a zoonotic disease with a canine urban reservoir in South America. Dogs from an endemic area within Brazil, which were naturally infected with Leishmania infantum, and those presenting severe clinical (SC), mild, or no clinical (MNC) disease, were evaluated. Parasite load, histopathology, and cytokine and iNOS mRNA expressions were assessed in the spleen and liver in order to determine the potential markers for disease susceptibility or resistance. As a result, dogs with both SC and MNC had high parasite loads; IFN-γ was the most expressive cytokine in both organs, along with IL-6 and IL-4 being detected in the spleen and liver, and IL-10 only in liver. The hepatic tissue presented higher medians for IFN-γ and IL-10, and was the main organ to produce cytokines with hepatic IL-10 suggesting a regulatory follow up. Granulomas were detected in both organs; however, when absent in spleen, they were associated with elevated IL-6 levels, thus highlighting the anti-inflammatory role of IL-6. Microscopic lesions in the spleen were predominantly characterized by an extensively disorganized white pulp and splenic response was suggested as sub optimized. Parasite load, tissue damage, and immunological response may vary in the dogs with similar clinical symptoms, which may not be a good parameter for assessing the animal’s susceptibility to VL.

scholarly journals Trichinella spiralis reinfection: changes in cellular and humoral immune response in BALB/c mice

2012 ◽  
Vol 49 (4) ◽  
pp. 201-210 ◽  
Author(s):  
E. Dvorožňáková ◽  
M. Kołodziej-Sobocińska ◽  
Z. Hurníková
Keyword(s):  
Immune Response ◽  
B Lymphocytes ◽  
Trichinella Spiralis ◽  
Parasite Burden ◽  
Humoral Response ◽  
T And B Lymphocytes ◽  
High Concentration ◽  
Immunological Parameters ◽  
Humoral Immune ◽  
Ifn Γ

AbstractTrichinella spiralis infection induces a host cell-mediated and humoral response. The role of T and B lymphocytes in the immune response of mice reinfected with 2 × 400 T. spiralis larvae was studied in relation to the parasite burden. BALB/c mice were infected on days 0 and 60 and immunological parameters were examined within a period of 180 days. In comparison with a single T. spiralis infection, T- and B-lymphocytes in reinfected mice responded by a significant increase in the proliferative activity during 10 days after reinfection. At the same time, the percentages of CD4+ T-cells of reinfected mice were also increased. In contrast, the CD8+ T-cell numbers were significantly reduced almost 30 days after reinfection. High concentration of serum IFN-γ lasted till the end of the experiment. The IL-5 level was increased only for 2 weeks after reinfection, followed by its decrease. Kinetics of specific anti-Trichinella immunoglobulins IgG2a was not affected with reinfection, but specific antibodies IgG1 significantly increased after reinfection and persisted elevated till the end of the experiment. Lower numbers of adults (69.2 % reduction) in the small intestine and 72.3 % reduction in muscle larvae were found after reinfection. Stimulation of the host immune response — the increased activity of CD4+ T lymphocytes and high levels of IFN-γ and specific IgG1 after reinfection, contributed to the reduction of the parasite burden.

High efficacy of a 20 amino acid peptide of the acidic ribosomal protein P0 against the cattle tick, Rhipicephalus microplus

2015 ◽  
Vol 6 (4) ◽  
pp. 530-537 ◽  
Author(s):  
Alina Rodríguez-Mallon ◽  
Pedro E. Encinosa ◽  
Lídice Méndez-Pérez ◽  
Yamil Bello ◽  
Rafmary Rodríguez Fernández ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ribosomal Protein ◽  
Rhipicephalus Microplus ◽  
Cattle Tick ◽  
High Efficacy ◽  
Amino Acid Peptide ◽  
Ribosomal Protein P0 ◽  
Acidic Ribosomal Protein
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