Comparative evaluation of phenol and thimerosal as preservatives for a candidate vaccine against American cutaneous leishmaniasis

Mayrink, Wilson; Tavares, Carlos Alberto Pereira; Deus, Rosângela Barbosa de; Pinheiro, Melina de Barros; Guimarães, Talita Antunes; Andrade, Hélida Monteiro de; Costa, Carlos Alberto da; Toledo, Vicente de Paulo Coelho Peixoto de

doi:10.1590/s0074-02762010000100013

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…The Montenegro skin test (MST), with a sensitivity rate of 86.4 up to 100% is the main diagnostic test in primary care (55) and is also positive in asymptomatic subjects indicating previous exposure to Leishmania infection but without disease (56, 57). Interestingly, in field assays of a crude vaccine against CL, vaccine efficacy was only detected among vaccinated individuals that showed positive MST to leishmanial antigen (58–60). Remarkably, the NH36-saponin vaccines induced strong IDR responses which were excellent correlates of protection against mice infected by L .…”

Section: Discussionmentioning

confidence: 99%

The F1F3 Recombinant Chimera of Leishmania donovani-Nucleoside Hydrolase (NH36) and Its Epitopes Induce Cross-Protection Against Leishmania (V.) braziliensis Infection in Mice

et al. 2019

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Leishmania ( V .) braziliensis is the etiological agent of Cutaneous (CL) and Mucocutaneous leishmaniasis (ML) in the New World. CL can be more benign but ML can be severe and disfiguring. Immunity to these diseases include hypersensitivity, an enhanced inflammatory response with strong IFN-γ and TNF-α secretion. Additionally, the production of IL-10 which down modulates the immune response is reduced. The Nucleoside hydrolase (NH36) of Leishmania ( L .) donovani is the main antigen of the Leishmune veterinary vaccine and its F3 domain induces a CD4 + T cell-mediated protection against L . ( L .) infantum chagasi infection. Prevention of L . ( L .) amazonensis infection requires in contrast an additional CD8 + T cell mediated response induced by the F1 domain. Consequently, the F1F3 recombinant chimera, which contains both domains cloned in tandem, optimized the vaccine efficacy against L . ( L .) amazonensis mouse infection. We compared the efficacies of NH36, F1, F3, and the FIF3 chimera against L . ( V .) braziliensis mouse infection. The F1F3 chimera increased the NH36 specific IgA and response before and after infection and the IgG and IgG3 levels after challenge. It also induced a 49% stronger intradermal response to leishmanial antigen (IDR) than NH36 that was positively correlated to the levels of IFN-γ and TNF-α, IgG, IgG2a, IgG2b, and IgG3 anti-NH36 antibodies. However, stronger Th1 responses with elevated IFN-γ / IL-10 and TNF-α / IL-10 ratios were promoted by the F3 and F1 vaccines and detected in infected controls while the F1F3 chimera promoted the highest IL-10 secretion, which reduced the pathological Th1 response, and characterized the induction of a mixed and/or T-cell regulatory response. We identified the epitopes responsible for these immune responses. The F3 vaccine induced the earliest immunity and after challenge, the F1F3 chimera promoted the highest CD4 + and CD8 + cytokine-secreting T cell responses, and the predominant frequencies of multifunctional CD4 + and CD8 + IL-2 + TNF-α + IFN-γ + T cells. Also as observed against L . ( L .) amazonensis infection, the F1F3 chimera showed the strongest reduction of the ear lesions sizes induced by L . ( V .) braziliensis . Our results confirm the potential use ...

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Section: Discussionmentioning

confidence: 99%

The F1F3 Recombinant Chimera of Leishmania donovani-Nucleoside Hydrolase (NH36) and Its Epitopes Induce Cross-Protection Against Leishmania (V.) braziliensis Infection in Mice

et al. 2019

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“…Geier et al [22] tested several compounds routinely used in the US; they reported that the concentration of Thimerosal necessary to induce bacterial cell-death was higher than that actually found in the US products. Furthermore, the phenolpreserved vaccine showed less proteolytic activity than the Thimerosal-preserved one [23]. Such relative limitations are now coupled with experimental studies consistently showing neural-cell toxicity caused by Thimerosal at concentrations relevant to vaccines.…”

Section: In Vitro Testsmentioning

confidence: 99%

Integrating Experimental (In Vitro and In Vivo) Neurotoxicity Studies of Low-dose Thimerosal Relevant to Vaccines

Dórea¹

2011

Neurochem Res

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There is a need to interpret neurotoxic studies to help deal with uncertainties surrounding pregnant mothers, newborns and young children who must receive repeated doses of Thimerosal-containing vaccines (TCVs). This review integrates information derived from emerging experimental studies (in vitro and in vivo) of low-dose Thimerosal (sodium ethyl mercury thiosalicylate). Major databases (PubMed and Web-of-science) were searched for in vitro and in vivo experimental studies that addressed the effects of low-dose Thimerosal (or ethylmercury) on neural tissues and animal behaviour. Information extracted from studies indicates that: (a) activity of low doses of Thimerosal against isolated human and animal brain cells was found in all studies and is consistent with Hg neurotoxicity; (b) the neurotoxic effect of ethylmercury has not been studied with co-occurring adjuvant-Al in TCVs; (c) animal studies have shown that exposure to Thimerosal-Hg can lead to accumulation of inorganic Hg in brain, and that (d) doses relevant to TCV exposure possess the potential to affect human neuro-development. Thimerosal at concentrations relevant for infants' exposure (in vaccines) is toxic to cultured human-brain cells and to laboratory animals. The persisting use of TCV (in developing countries) is counterintuitive to global efforts to lower Hg exposure and to ban Hg in medical products; its continued use in TCV requires evaluation of a sufficiently nontoxic level of ethylmercury compatible with repeated exposure (co-occurring with adjuvant-Al) during early life.

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Chemical diversity and potential biological functions of the pygidial gland secretions in two species of Neotropical dung roller beetles

et al. 2015

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Dung roller beetles of the genus Canthon (Coleoptera: Scarabaeinae) emit an odorous secretion from a pair of pygidial glands. To investigate the chemical composition of these secretions, we used stir bar sorptive extraction (SBSE), coupled with gas chromatography-mass spectrometry (GC-MS) for analysis of extracts of pygidial gland secretions secreted by the dung roller beetles Canthon femoralis femoralis and Canthon cyanellus cyanellus. Chemical analyses of volatiles collected from pygidial gland secretions comprise a great diversity of the functional groups. Chemical profile comparisons showed high intra-and interspecific variability. The pygidial gland secretion of Canthon f. femoralis was dominated by sesquiterpene hydrocarbons, whereas the profile of Canthon c. cyanellus was dominated by carboxylic acids. The different pygidial secretions have a high diversity of chemical compounds suggesting a multifunctional nature involving some key functions in the biology. We discuss the biological potential of these compounds found in the pygidial glands of each species with respect to their ecological and behavioral relevance.

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Comparative evaluation of phenol and thimerosal as preservatives for a candidate vaccine against American cutaneous leishmaniasis

Cited by 6 publications

References 20 publications

The F1F3 Recombinant Chimera of Leishmania donovani-Nucleoside Hydrolase (NH36) and Its Epitopes Induce Cross-Protection Against Leishmania (V.) braziliensis Infection in Mice

The F1F3 Recombinant Chimera of Leishmania donovani-Nucleoside Hydrolase (NH36) and Its Epitopes Induce Cross-Protection Against Leishmania (V.) braziliensis Infection in Mice

Integrating Experimental (In Vitro and In Vivo) Neurotoxicity Studies of Low-dose Thimerosal Relevant to Vaccines

Chemical diversity and potential biological functions of the pygidial gland secretions in two species of Neotropical dung roller beetles

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