Immune protection conferred by recombinant MRLC (myosin regulatory light chain) antigen in TiterMax Gold® adjuvant against experimental fasciolosis in rats

Henker, Luan Cleber; Schwertz, Claiton I.; Lucca, Neuber J.; Piva, Manoela Marchezan; Prior, Keila Catarina; Bąska, Piotr; Norbury, Luke J.; Januszkiewicz, Kamil; Dezen, Diogenes; Moresco, Rafael Noal; Rosa, Liana Bertagnolli da; Mendes, Ricardo E.

doi:10.1016/j.vaccine.2016.11.092

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…It was remarkable that at 1, 3, and 9 dpi gene expression for TNF-α was higher in group 1 (immunized) than in group 2 (infected control), despite the vaccine being non-protective. This finding agrees with the higher TNF-α expression in liver tissues from rats immunized with the myosin regulatory light chain (MRLC) of F. hepatica and partially protected compared to unimmunized rats in chronic infections, coinciding with lower hepatic lesions in immunized rats [ 37 ]. By contrast, in the present study, immunized sheep did not show fluke burden reduction, but a reduction of gross hepatic lesions was found at 9 dpi in immunized sheep compared to unimmunized and infected animals [ 13 ].…”

Section: Discussionsupporting

confidence: 80%

Fasciola hepatica induces Foxp3 T cell, proinflammatory and regulatory cytokine overexpression in liver from infected sheep during early stages of infection

Pacheco

Abril

Zafra

et al. 2018

Vet Res

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The expression of T regulatory cells (Foxp3), regulatory (interleukin [IL]-10 and transforming growth factor beta [TGF-β]) and proinflammatory (tumor necrosis factor alpha [TNF-α] and interleukin [IL]-1β) cytokines was quantified using real time polymerase chain reaction (qRT-PCR) in the liver of sheep during early stages of infection with Fasciola hepatica (1, 3, 9, and 18 days post-infection [dpi]). Portal fibrosis was also evaluated by Masson’s trichrome stain as well as the number of Foxp3+ cells by immunohistochemistry. Animals were divided into three groups: (a) group 1 was immunized with recombinant cathepsin L1 from F. hepatica (FhCL1) in Montanide adjuvant and infected; (b) group 2 was uniquely infected with F. hepatica; and (c) group 3 was the control group, unimmunized and uninfected. An overexpression of regulatory cytokines of groups 1 and 2 was found in all time points tested in comparison with group 3, particularly at 18 dpi. A significant increase of the number of Foxp3+ lymphocytes in groups 1 and 2 was found at 9 and 18 dpi relative to group 3. A progressive increase in portal fibrosis was found in groups 1 and 2 in comparison with group 3. In this regard, group 1 showed smaller areas of fibrosis than group 2. There was a significant positive correlation between Foxp3 and IL-10 expression (by immunohistochemistry and qRT-PCR) just as between portal fibrosis and TGF-β gene expression. The expression of proinflammatory cytokines increased gradually during the experience. These findings suggest the induction of a regulatory phenotype by the parasite that would allow its survival at early stages of the disease when it is more vulnerable.

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Section: Discussionsupporting

confidence: 80%

Fasciola hepatica induces Foxp3 T cell, proinflammatory and regulatory cytokine overexpression in liver from infected sheep during early stages of infection

Pacheco

Abril

Zafra

et al. 2018

Vet Res

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“…Furthermore, the exposure of the epitopes observed in Ol-MJA 3D structure may support the immunological potential of this protein. In addition, the immunogenicity of Ol-MJA may be also reinforced by the partial 3D structure homology with those of other myosin-like proteins (i.e., tropomyosin, myosin, actin), as previously described for Schistosoma mansoni [57] and for Fasciola hepatica, the latter conferring protection in F. hepatica experimentally infected rats [58].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 68%

Major antigen and paramyosin proteins as candidate biomarkers for serodiagnosis of canine infection by zoonotic Onchocerca lupi

et al. 2021

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Onchocerca lupi (Spirurida: Onchocercidae) is a filarial worm parasitizing domestic carnivores and humans. Adult nematodes usually localize beneath in the sclera or in the ocular retrobulbar of infected animals, whilst microfilariae are found in the skin. Therefore, diagnosis of O. lupi is achieved by microscopic and/or molecular detection of microfilariae from skin biopsy and/or surgical removal of adults from ocular tissues of infected hosts. An urgent non-invasive diagnostic tool for the diagnosis of O. lupi in dog is mandatory. In this study, an immunoproteomic analyses was performed using a combination of immunoblotting and mass spectrometry techniques. Onchocerca lupi major antigen (Ol-MJA) and paramyosin (Ol-PARA) proteins were identified as potential biomarkers for serodiagnosis. Linear epitopes were herein scanned for both proteins using high-density peptide microarray. Sera collected from dog infected with O. lupi and healthy animal controls led to the identification of 11 immunodominant antigenic peptides (n = 7 for Ol-MJA; n = 4 for Ol-PARA). These peptides were validated using sera of dogs uniquely infected with the most important filarioids infesting dogs either zoonotic (Dirofilaria repens, Dirofilaria immitis) or not (Acanthocheilonema reconditum and Cercopithifilaria bainae). Overall, six antigenic peptides, three for Ol-MJA and for Ol-PARA, respectively, were selected as potential antigens for the serological detection of canine O. lupi infection. The molecular and proteomic dataset herein reported should provide a useful resource for studies on O. lupi toward supporting the development of new interventions (drugs, vaccines and diagnostics) against canine onchocercosis.

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“…TiterMax Gold ® is an effective adjuvant to enhance cellular and humoral immune response in animal studies, as an alternative to Complete Freund’s Adjuvant due to safer and easier use. The immunol potency of the TiterMax Gold ® adjuvant depends on a stable water-in-oil emulsion, which capsulates into effective antigens derived from pathogens [ 171 ]. The TiterMax adjuvant is often used as an alternative to CFA since it produces a similar antibody titre, although TiterMax has been shown to induce immunisation-elicited lesions [ 158 ].…”

Section: Emulsions Adjuvantsmentioning

confidence: 99%

“…Henker et al subcutaneously immunized rats with recombinant myosin regulatory light chain capsulated into TiterMax Gold ® adjuvant. This study indicated the significant reduction in fluke burdens of 61.5% ( p < 0.001) compared with the no adjuvanted groups, with mixed Th1/Th2 immune responses [ 171 ]. Further, assessment of TiterMax ® adjuvant as part of an anti-Schistosoma vaccine by Leite and colleagues indicated a stronger recruitment of mast cells and basophils produced, leading to more IgG2a antibodies [ 12 ].…”

Section: Emulsions Adjuvantsmentioning

confidence: 99%

Advances in Infectious Disease Vaccine Adjuvants

et al. 2022

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Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases. Immune stimulants (or adjuvants) are an indispensable factor in vaccine development, especially for inactivated and subunit-based vaccines due to their decreased immunogenicity compared to whole pathogen vaccines. Adjuvants are widely diverse in structure; however, their overall function in vaccine constructs is the same: to enhance and/or prolong an immunological response. The potential for adverse effects as a result of adjuvant use, though, must be acknowledged and carefully managed. Understanding the specific mechanisms of adjuvant efficacy and safety is a key prerequisite for adjuvant use in vaccination. Therefore, rigorous pre-clinical and clinical research into adjuvant development is essential. Overall, the incorporation of adjuvants allows for greater opportunities in advancing vaccine development and the importance of immune stimulants drives the emergence of novel and more effective adjuvants. This article highlights recent advances in vaccine adjuvant development and provides detailed data from pre-clinical and clinical studies specific to infectious diseases. Future perspectives into vaccine adjuvant development are also highlighted.

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Immune protection conferred by recombinant MRLC (myosin regulatory light chain) antigen in TiterMax Gold® adjuvant against experimental fasciolosis in rats

Cited by 5 publications

References 45 publications

Fasciola hepatica induces Foxp3 T cell, proinflammatory and regulatory cytokine overexpression in liver from infected sheep during early stages of infection

Fasciola hepatica induces Foxp3 T cell, proinflammatory and regulatory cytokine overexpression in liver from infected sheep during early stages of infection

Major antigen and paramyosin proteins as candidate biomarkers for serodiagnosis of canine infection by zoonotic Onchocerca lupi

Advances in Infectious Disease Vaccine Adjuvants

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