Identification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells: Towards the development of a multi-epitope vaccine

Thema, N.; Tshilwane, Selaelo Ivy; Pretorius, Ashley; Sơn, Lê Văn; Smith, R.M.; Steyn, H.C.; Liebenberg, Junita; Kleef, Mirinda Van

doi:10.1016/j.molimm.2018.12.012

Cited by 7 publications

(11 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, an increase in the IFN-γ level can lead to activation of Tc, natural killer (NK), and opsonin antibodies, such as IgG2a (35). On the other hand, increased level of cytokines, such as IL-4 and interleukin 23(IL-23) against immunological agents can lead to the altered immune responses to Th2 and IgG1 antibodies (12,36).…”

Section: Discussionmentioning

confidence: 99%

“…If the appropriate antigen is selected, one can hope to produce an effective vaccine (11). A de nite approach to select the strong and effective antigens is predicting the antigenic epitopes proven in the previous studies to have an immunogenic effect, but it does not have the potential to become an effective vaccine due to the mentioned reasons (12). Also, adding a linker can be very helpful for enhancing the immunogenicity of the vaccines.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

Rabienia

Roudbari

Ghanbariasad

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Nowadays, the prevention of parasitic diseases including leishmaniasis is one of the health concerns in the world, and cutaneous leishmaniasis is the most common type of these diseases. So far, no drug or vaccine has been approved for definitive treatment of this disease.Methods: In this study, the recombinant lentiviral vaccine containing a new multi-epitope of KMP11 and HASPB of the Leishmania major (L. major) was synthesized that had previously been designed in-silico. The designed multi-epitope was subcloned into the pCDH513 lentiviral vector, and the recombinant lentiviral multi-epitope vaccine (rLV-multi-epitope) was synthesized in the HEK293T cell by the packaging vectors. Also, the Western Blotting method was used to confirm the gene expression. Then, the rLV-multi-epitope vaccine was injected twice, along with two control groups, PBS, and rLV-empty to immunize the BALB /c mice. Twenty-one days after the second injection, the splenocytes of the mice were isolated and stimulated with the Leishmania lysate.Results: The results of the enzyme-linked immunoassay (ELISA) test not only showed the titer of IFN-γ and IL-4 was increased in the immunized group compared to the controls, but also indicated that the ratio of IFN-γ to IL-4 cytokines in the main group was increased significantly. As a result, the Th1 response was generated in the main group. Moreover, the humoral immune response was assessed and the results showed that the ratio of IgG2a to IgG1 antibody in the sera of the immunized mice was increased compared to the control groups. Also, the ratio of IgG2a to IgG1 was increased in the main group. Therefore, the humoral immune response was increased, which can also have a positive effect on increasing the Th1 response.Conclusions: Our results showed that immunization by the new rLV-multi-epitope vaccine could stimulate the immune system towards the Th1 through increasing the IFN-γ production.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

Rabienia

Roudbari

Ghanbariasad

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In order to identify CD4 + Th1 epitopes inducing IFN-γ production, a screening of ten E. ruminantium proteins (Erum0660, Erum1150, Erum2540, Erum5420, Erum7140, Erum7320, Erum7350, Erum7360, Erum7620 and Erum8010) previously identified as immunogenic was carried out to determine their ability to induce cellular immunity in sheep [34]. The authors identified 23 peptides stimulating different cell-mediated immune responses.…”

Section: Ehrlichia Sppmentioning

confidence: 99%

“…Stimulation of memory CD4 + T cells proliferation and IFN-γ production in immune sheep Peripheral blood mononuclear cell (PBMCs) [34] Outer…”

Section: Theileria Sppmentioning

confidence: 99%

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

Torina

Blanda

Villari

et al. 2020

IJMS

View full text Add to dashboard Cite

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens.

show abstract

“…The 1H12 cocktail DNA vaccine containing four E. ruminantium genes provided 100% protection against a virulent needle challenge in sheep (Collins et al 2003 ) but only 20% protection in sheep to a natural tick challenge in the field (Pretorius et al 2008 ). Thereafter, selected 1H12 epitopes and multiple-vaccine candidate E. ruminantium epitopes that induce varied cellular immune responses (Thema et al 2019a , 2019b ) were combined in a multi-epitope DNA vaccine. This vaccine induced 60% protective efficacy in sheep after a laboratory tick challenge (Tshilwane et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Th1 and Th2 epitopes of Cowdria polymorphic gene 1 of Ehrlichia ruminantium

Ngoepe¹,

Pretorius²,

Steyn³

et al. 2023

Onderstepoort j. vet. res.

View full text Add to dashboard Cite

Cowdria polymorphic gene 1 (cpg1, Erum2510, ERUM_RS01380) has been shown to induce 30% and 100% protection in sheep immunised by deoxyribonucleic acid (DNA) prime combined with DNA boost and DNA prime combined with protein boost, respectively, against heartwater infection via needle challenge. To localise its antigenic regions for inclusion in a multi-epitope DNA vaccine against heartwater, Erum2510 was cleaved into five overlapping subfragments. These subfragments were expressed individually in an Escherichia coli host expression system and evaluated for their ability to induce proliferative responses, Th1 and Th2 cytokines (interferon gamma [IFN-γ] and interleukin 4 [IL-4]) via enzyme-linked immunospot (ELISpot), quantitative real time polymerase chain reaction (qRT-PCR) and flow cytometry. Recombinant (r)proteins 3 and 4 were shown to induce immunodominant Th1 and Th2 immune responses characterised by the secretion of effector cytokines IFN-γ and IL-4 in addition to differential messenger ribonucleic acid (mRNA) expression of tumour necrosis factor (TNF), IL-2, IL-1, IL-18, IL-10, transforming growth factor (TGF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and inducible nitric oxide synthase (iNOS). Thirty-seven overlapping synthetic peptides (16 mer) spanning the lengths of these immunodominant rproteins were synthesised and assayed. A peptide pool comprising p9 and p10 derived from rprotein 3 induced a Th1-biased immune response. A peptide pool comprising p28 and p29 derived from rprotein 4 induced a mixed Th1 and Th2 immune response characterised by secretion of IFN-γ and differential mRNA expression of IL-1, IL-2, IL-10, IL-12, iNOS, TGF, TNF and GM-CSF. Only one of the peptides (p29) induced secretion of IL-4. Phenotypic analysis showed significant activation of cluster of differentiation 8+ (CD8+), cluster of differentiation 4+ (CD4+) and B+ lymphocyte populations. Findings suggest that Erum2510 rproteins and synthetic peptides can induce both cellular and humoral immune responses, thereby implicating their importance in protection against heartwater.Contribution: This study will facilitate the design of an effective multi-epitope DNA vaccine against heartwater that will contribute to control this economically important disease in sub-Saharan Africa and beyond.

show abstract

Identification and characterisation of conserved epitopes of E. ruminantium that activate Th1 CD4+ T cells: Towards the development of a multi-epitope vaccine

Cited by 7 publications

References 75 publications

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

Th1 and Th2 epitopes of Cowdria polymorphic gene 1 of Ehrlichia ruminantium

Contact Info

Product

Resources

About