Despite Leishvaccine and Leishmune® trigger distinct immune profiles, their ability to activate phagocytes and CD8+ T-cells support their high-quality immunogenic potential against canine visceral leishmaniasis

Araújo, Márcio Sobreira Silva; Andrade, Renata Aline de; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Sathler-Avelar, Renato; Teixeira-Carvalho, Andréa; Andrade, Mariléia Cháves; Mello, M. N.; Martins‐Filho, Olindo Assis

doi:10.1016/j.vaccine.2008.02.044

Cited by 32 publications

(32 citation statements)

References 60 publications

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“…marker, but an overall unaltered expression of CD3 ? , has been previously described [25]. It has been suggested that the CD5 Low?…”

Section: Discussionmentioning

confidence: 92%

“…Immunophenotyping of canine whole blood leukocytes by flow cytometry Immunophenotyping analyses of canine peripheral blood through flow cytometry were carried out as described by Araujo et al [25]. Briefly, using 12 mm975 mm polystyrene tubes, 30 ll aliquots of whole EDTA peripheral blood were incubated at room temperature (RT) for 30 min, in the dark, with 30 ll of fluorochrome-labeled anti-canine cell surface marker monoclonal antibodies (mAbs), previously diluted in PBS-W (phosphate buffered saline 0.15 M, pH 7.2, supplemented with 0.5% of bovine seric albumin and 0.1% of sodium azide, all purchased from Sigma, St Louis, MO, USA).…”

Section: Blood Samplesmentioning

confidence: 99%

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Understanding of the immunological heterogeneity of canine mammary carcinomas to provide immunophenotypic features of circulating leukocytes as clinically relevant prognostic biomarkers

Estrela‐Lima

Araújo²,

Costa-Neto

et al. 2011

Breast Cancer Res Treat

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We have evaluated the phenotypic features of peripheral blood leukocytes as putative novel biomarkers with prognostic values to monitor canine mammary carcinomas. Female dogs were categorized into distinct groups, referred as mammary carcinoma in benign mixed tumor-MC-BMT and mammary carcinoma-MC. Our findings demonstrate that decreased percentage of B-cells along with increased frequency of NK-cells, CD8(+)T-cells, and CD8(+)CD5(Low+)T-cells beside higher T/B-cells and lower CD4(+)/CD8(+) ratio were the hallmarks of MC-BMT. Despite the lower expression of MHCI and MHCII, the lymphocytes from MC-BMT and MC displayed higher migration potential as suggested by enhanced frequency of CD18(+) events. Although increased levels of macrophage-like cells/(CD14(+)CD16(+)) and decreased levels of MHCII expression were a common phenotypic feature in mammary carcinoma, down-regulation of MHCI was selectively observed in MC. Decreased frequency of CD4(+) T-cells with increased levels of CD8(+) T-cells and lower CD4(+)/CD8(+) T-cell ratio were relevant biomarkers of MC-BTM(-). Although decreased expression of MHCI by monocytes was observed in MC-BTM regardless of the presence of lymph node metastasis, this phenotypic feature was restricted to MC free of metastasis. The CD4(+)/CD8(+) T-cells ratio lower than 1.8 was elected as a valid parameter with outstanding performance to predict survival in MC-BMT. On the other hand, the MHCI expression by monocytes higher than 10(2) MFI showed good value to estimate worse outcome in MC. These results should help to improve our understanding of the immunological heterogeneity of canine mammary carcinomas and provide tools for the determination of cut-off scores of clinically relevant immonophenotypic prognostic biomarkers.

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“…marker, but an overall unaltered expression of CD3 ? , has been previously described [25]. It has been suggested that the CD5 Low?…”

Section: Discussionmentioning

confidence: 92%

Section: Blood Samplesmentioning

confidence: 99%

Understanding of the immunological heterogeneity of canine mammary carcinomas to provide immunophenotypic features of circulating leukocytes as clinically relevant prognostic biomarkers

Estrela‐Lima

Araújo²,

Costa-Neto

et al. 2011

Breast Cancer Res Treat

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“…The strong immunogenicity induced by Leishmune® vaccine was demonstrated by the seropositivity, increased positive DTH responses and average increase in CD8 + and CD21 + cells. Recently, immunization with Leishmune® induced an immunological pattern characterized by activation of CD8 + cells and enhanced levels of IFN-γ, NO and IgG2 [167,168]. The potential effect of Leishmune® vaccine to block the transmission of Leishmania parasite in dogs was also investigated [169].…”

Section: Fmlmentioning

confidence: 99%

Vaccine candidates for leishmaniasis: A review

Nagill

Kaur

2011

International Immunopharmacology

109

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“…Recently, we developed the first licensed second generation vaccine against canine VL leishmaniasis (Leishmune ® ), which contains the fucose–mannose ligand (FML) antigen of L. donovani in formulation with saponin (16–19), is a transmission blocking vaccine (18, 19) and has already determined a reduction in the incidence of the human and canine disease in Brazilian endemic areas (20). Prophylactic vaccination of dogs with Leishmune ® promoted increases in the production of NO, IgG2 antibodies against FML and L. chagasi , intradermal reactions and proportions of CD8 + lymphocytes, which secrete more IFN-γ than IL-4 (21, 22) expressing a selective pro-inflammatory pattern (IFN-γ/NO) (23). The early and persistent activation of neutrophils and monocytes have also been described (23).…”

Section: Introductionmentioning

confidence: 99%

Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy Against Leishmania amazonensis Murine Infection

et al. 2014

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Nucleoside hydrolases of the Leishmania genus are vital enzymes for the replication of the DNA and conserved phylogenetic markers of the parasites. Leishmania donovani nucleoside hydrolase (NH36) induced a main CD4+ T cell driven protective response against L. chagasi infection in mice which is directed against its C-terminal domain. In this study, we used the three recombinant domains of NH36: N-terminal domain (F1, amino acids 1–103), central domain (F2 aminoacids 104–198), and C-terminal domain (F3 amino acids 199–314) in combination with saponin and assayed their immunotherapeutic effect on Balb/c mice previously infected with L. amazonensis. We identified that the F1 and F3 peptides determined strong cross-immunotherapeutic effects, reducing the size of footpad lesions to 48 and 64%, and the parasite load in footpads to 82.6 and 81%, respectively. The F3 peptide induced the strongest anti-NH36 antibody response and intradermal response (IDR) against L. amazonenis and a high secretion of IFN-γ and TNF-α with reduced levels of IL-10. The F1 vaccine, induced similar increases of IgG2b antibodies and IFN-γ and TNF-α levels, but no IDR and no reduction of IL-10. The multiparameter flow cytometry analysis was used to assess the immune response after immunotherapy and disclosed that the degree of the immunotherapeutic effect is predicted by the frequencies of the CD4+ and CD8+ T cells producing IL-2 or TNF-α or both. Total frequencies and frequencies of double-cytokine CD4 T cell producers were enhanced by F1 and F3 vaccines. Collectively, our multifunctional analysis disclosed that immunotherapeutic protection improved as the CD4 responses progressed from 1+ to 2+, in the case of the F1 and F3 vaccines, and as the CD8 responses changed qualitatively from 1+ to 3+, mainly in the case of the F1 vaccine, providing new correlates of immunotherapeutic protection against cutaneous leishmaniasis in mice based on T-helper TH1 and CD8+ mediated immune responses.

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Despite Leishvaccine and Leishmune® trigger distinct immune profiles, their ability to activate phagocytes and CD8+ T-cells support their high-quality immunogenic potential against canine visceral leishmaniasis

Cited by 32 publications

References 60 publications

Understanding of the immunological heterogeneity of canine mammary carcinomas to provide immunophenotypic features of circulating leukocytes as clinically relevant prognostic biomarkers

Understanding of the immunological heterogeneity of canine mammary carcinomas to provide immunophenotypic features of circulating leukocytes as clinically relevant prognostic biomarkers

Vaccine candidates for leishmaniasis: A review

Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy Against Leishmania amazonensis Murine Infection

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