Heterologous priming–boosting with DNA and vaccinia virus expressing kinetoplastid membrane protein-11 induces potent cellular immune response and confers protection against infection with antimony resistant and sensitive strains of Leishmania (Leishmania) donovani

Guha, Rajan; Das, Suvadra; Ghosh, June; Naskar, Kshudiram; Mandala, Ashok; Sundar, Shyam; Dujardin, Jean Claude; Roy, Syamal

doi:10.1016/j.vaccine.2013.02.025

Cited by 37 publications

(17 citation statements)

References 48 publications

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“…This is the first time this protein has been used as a vaccine against VL. KMP‐11, which is a highly conserved surface membrane protein present in all kinetoplastid protozoa, is considered a potential vaccine candidate for leishmaniasis. This protein has strong antigenicity for murine and human T cells and is capable of stimulating both innate and adaptive immune responses …”

Section: Introductionmentioning

confidence: 99%

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

Fan²,

Zhang

et al. 2018

Immunology

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Summary Visceral leishmaniasis is a tropical and neglected disease with an estimated 200 000–400 000 cases and 60 000 deaths worldwide each year. Currently, no clinically valid vaccine is available for this disease. In this study, we formulated DNA and protein vaccines encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis. We predicted the secondary and tertiary structures, surface properties, subcellular localization, potential binding sites and HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2. The best candidate CpG ODN (2395, M362, D‐SL03 or 685) was screened out as a DNA vaccine adjuvant. We also prepared Kmp‐11 and Kmp‐11/CaNA2 DNA and protein vaccines, respectively, for comparison. BALB/c mice were immunized with a DNA prime‐protein boost immunization strategy and challenged with a newly isolated Leishmania strain from an individual with visceral leishmaniasis. The IgG antibody titers showed that our vaccine had strong immunogenicity with a long duration, especially cellular immunity. The spleen parasite burden of each group demonstrated that the CaNA2 vaccine had a certain immune protective effect on visceral leishmaniasis in BALB/c mice, and the amastigote reduction rate reached 76%. Preliminary safety tests confirmed the safety of the vaccine. Our work demonstrates that the HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitope CaNA2 DNA prime‐protein boost vaccine may be a safe and effective epitope vaccine candidate against visceral leishmaniasis.

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Section: Introductionmentioning

confidence: 99%

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

Fan²,

Zhang

et al. 2018

Immunology

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“…Presence of these Treg cells during these infections becomes an important barrier for any vaccination or other treatment strategies [45]. A successful vaccine against Leishmaniasis is still elusive despite several recent encouraging reports [46]–[48] and success of such vaccine depends on the IL-10 production by Treg cells [49]. Presence of Treg cells and associated IL-10 production is reported in reactivation of disease in the form of PKDL [50].…”

Section: Discussionmentioning

confidence: 99%

Antimony Resistant Leishmania donovani but Not Sensitive Ones Drives Greater Frequency of Potent T-Regulatory Cells upon Interaction with Human PBMCs: Role of IL-10 and TGF-β in Early Immune Response

et al. 2014

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In India the sand fly, Phlebotomus argentipes, transmitted parasitic disease termed kala-azar is caused by Leishmania donovani (LD) in humans. These immune-evading parasites have increasingly developed resistance to the drug sodium antimony gluconate in endemic regions.Lack of early diagnosis methods for the disease limits the information available regarding the early interactions of this parasite with either human tissues or cell lineages. We reasoned that peripheral blood mononuclear cells (PBMCs) from healthy human beings could help compare some of their immune signatures once they were exposed for up to 8 days, to either pentavalent antimony sensitive (SbS-LD) or resistant (SbR-LD) Leishmania donovani isolates.At day 2, PBMC cultures exposed to SbS-LD and SbR-LD stationary phase promastigotes had four and seven fold higher frequency of IL-10 secreting monocyte-macrophage respectively, compared to cultures unexposed to parasites. Contrasting with the CD4+CD25−CD127− type-1 T-regulatory (Tr1) cell population that displayed similar features whatever the culture conditions, there was a pronounced increase in the IL-10 producing CD4+CD25+CD127low/− inducible T-regulatory cells (iTregs) in the PBMC cultures sampled at day 8 post addition of SbR-LD.Sorted iTregs from different cultures on day 8 were added to anti-CD3/CD28 induced naïve PBMCs to assess their suppressive ability. We observed that iTregs from SbR-LD exposed PBMCs had more pronounced suppressive ability compared to SbS-LD counterpart on a per cell basis and is dependent on both IL-10 and TGF-β, whereas IL-10 being the major factor contributing to the suppressive ability of iTregs sorted from PBMC cultures exposed to SbS–LD. Of note, iTreg population frequency value remained at the basal level after addition of genetically modified SbR-LD lacking unique terminal sugar in surface glycan.Even with limitations of this artificial in vitro model of L. donovani-human PBMC interactions, the present findings suggest that SbR-LD have higher immunomodulatory capacity which may favour aggressive pathology.

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“…We previously found the F3+GLA-SE vaccine to be protective in a mouse model of VL and, based on cell depletion studies, that protection was dependent on CD4 T cells; the vaccine did not generate a CD8 T cell response (18). Other vaccines tested in mouse models of VL that induced protection generated both a CD4 and CD8 T cell response; however, cell depletion studies were not conducted and protection could not be ascribed to any particular cell type (15–17). Given that roles for both CD4 and CD8 T cells in the control of Leishmania infection have been described, a prudent and practical vaccine strategy may involve generation of both T cell types.…”

Section: Discussionmentioning

confidence: 99%

“…donovani infection also lends itself to understanding how to generate both CD4 and CD8 T cells that are antigen specific and functionally protective. Several vaccines that elicit CD4 or CD8 T cell responses have demonstrated protection in mouse models of VL, but the specific contribution of each cell type is generally unclear (15–17). We recently reported that a chimeric protein expressed from a fusion of two Leishmania genes, named F3, when formulated with GLA-SE, a synthetic Toll-like receptor 4 (TLR4) agonist in an oil-in-water stable emulsion, generated F3-specific, CD4 T cell-dependent protection in a mouse model of L.…”

Section: Introductionmentioning

confidence: 99%

Optimizing Immunization Strategies for the Induction of Antigen-Specific CD4 and CD8 T Cell Responses for Protection against Intracellular Parasites

Hofmeyer

Duthie

Laurance

et al. 2016

Clin Vaccine Immunol

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Immunization strategies that generate either CD4 or CD8 T cell responses are relatively well described, but less is known with regard to optimizing regimens to induce both CD4 and CD8 memory T cells. Considering the importance of both CD4 and CD8 T cells in the control of intracellular pathogens such as Leishmania donovani, we wanted to identify vaccines that could raise both CD4 and CD8 T cell responses and determine how to configure immunization strategies to generate the best combined protective T cell response. We examined responses generated against the Leishmania vaccine antigen F3 following its administration in either recombinant form with the Toll-like receptor 4 (TLR4) agonist-containing adjuvant formulation GLA-SE (F3+GLA-SE) or as a gene product delivered in an adenoviral vector (Ad5-F3). Homologous immunization strategies using only F3+GLA-SE or Ad5-F3 preferentially generated either CD4 or CD8 T cells, respectively. In contrast, heterologous strategies generated both antigen-specific CD4 and CD8 T cells. Administration of F3+GLA-SE before Ad5-F3 generated the greatest combined CD4 and CD8 responses. Cytotoxic CD8 T cell responses were highest when Th1 cells were generated prior to their induction by Ad5-F3. Finally, a single immunization with a combination of F3+GLA-SE mixed with Ad5-F3 was found to be sufficient to provide protection against experimental L. donovani infection. Taken together, our data delineate immunization regimens that induce antigen-specific CD4 and CD8 T cell memory responses, and identify a single immunization strategy that could be used to rapidly provide protection against intracellular pathogens in regions where access to health care is limited or sporadic.

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Heterologous priming–boosting with DNA and vaccinia virus expressing kinetoplastid membrane protein-11 induces potent cellular immune response and confers protection against infection with antimony resistant and sensitive strains of Leishmania (Leishmania) donovani

Cited by 37 publications

References 48 publications

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

DNA prime‐protein boost vaccine encoding HLA‐A2, HLA‐A24 and HLA‐DR1 restricted epitopes of CaNA2 against visceral leishmaniasis

Antimony Resistant Leishmania donovani but Not Sensitive Ones Drives Greater Frequency of Potent T-Regulatory Cells upon Interaction with Human PBMCs: Role of IL-10 and TGF-β in Early Immune Response

Optimizing Immunization Strategies for the Induction of Antigen-Specific CD4 and CD8 T Cell Responses for Protection against Intracellular Parasites

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