The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis.

Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria. The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107-121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107-121) significantly reduced worm burden (48-50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107-121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis.

Chemotherapy-induced peripheral neuropathy: review for clinical practice / Neuropatia periférica induzida por quimioterapia: revisão para a prática clínica

ABSTRACTBACKGROUND AND OBJECTIVES:Chemotherapy-induced peripheral neuropathy is the most common neurological syndrome secondary to antineoplastic therapy primarily affecting patients being treated with taxanes and platinum derivatives. Sensory neuropathy is the most frequent type. This study aimed at carrying out a narrative review of the literature on the pathophysiology, clinical manifestations, impact, evaluation, diagnosis treatment and prevention of chemotherapy-induced peripheral neuropathy.CONTENTS:Recent studies have shown association among inflammatory molecules, oxidative stress and development of chemotherapy-induced peripheral neuropathy. Most frequent symptoms are limbs numbness and tingling, with neuropathic pain having significant impact on the functionality of patients submitted to antineoplastic therapy. Several evaluation tools have been tested, being electroneuromyography considered the golden standard for chemotherapy-induced peripheral neuropathy diagnosis. There are different pharmacological strategies for its therapy and prevention.CONCLUSION:It is known that chemotherapy-induced peripheral neuropathy is a frequent syndrome negatively interfering with cancer patients’ treatment and quality of life. Different drugs are associated to different risk levels, which show its neurobiological complexity. Prevention, diagnostic and treatment strategies have to greatly evolve to minimize its frequency and severity.

RESUMOJUSTIFICATIVA E OBJETIVOS:A neuropatia periférica induzida por quimioterapia é a síndrome neurológica mais comum secundária à terapêutica antineoplásica e acomete principalmente pacientes que necessitam de tratamento com taxanes e derivados da platina. A neuropatia sensorial é o tipo mais frequente. O objetivo deste estudo foi realizar uma revisão narrativa de literatura sobre a fisiopatologia, manifestações clínicas, impacto, avaliação, diagnóstico, tratamento e prevenção da neuropatia periférica induzida por quimioterapia.CONTEÚDO:Estudos recentes têm demonstrado associação entre moléculas inflamatórias, estresse oxidativo e o desenvolvimento da neuropatia periférica induzida por quimioterapia. Dentre os sintomas, queixas de dormências e formigamentos nos membros são as mais frequentes, sendo a dor neuropática quadro de significativo impacto na funcionalidade dos pacientes em terapia antineoplásica. Diversos instrumentos de avaliação têm sido testados, sendo a eletroneuromiografia considerada o padrão ouro para o diagnóstico de neuropatia periférica induzida por quimioterapia. A terapêutica e a sua prevenção contam com diferentes estratégias farmacológicas.CONCLUSÃO:Reconhece-se que a neuropatia periférica induzida por quimioterapia é uma síndrome frequente e que interfere negativamente no tratamento e na qualidade de vida do paciente com câncer. Fármacos diferentes estão associados a graus variáveis de risco, o que mostra sua complexidade neurobiológica. As estratégias de prevenção, diagnóstico e tratamento precisam evoluir sobremaneira no sentido de minimizar a sua ocorrência e a gravidade.

Profile of total IgG, IgG1, IgG2, IgG3 and IgG4 levels in sera of patients with paracoccidioidomycosis: treatment follow-up using Mexo and rPb27 as antigens in an ELISA.

The levels of total of IgG, IgG1, IgG2, IgG3 and IgG4 were evaluated in 54 patients with chronic paracoccidioidomycosis (PCM) before, during and after treatment using an enzyme-linked immunosorbent assay with Mexo and recombinant Pb27 (rPb27) as the antigens. Mexo was effective in distinguishing PCM patients from individuals in the negative control group (NC) based on total IgG and rPb27 performed worse than Mexo when these two groups were compared. IgG1, IgG2, IgG3 and IgG4 could not be used to clearly distinguish PCM patients from those in the NC group using either antigen. There was no clear relationship between antibody levels and the period of treatment. The majority of patients presented with decreased antibody levels during treatment, with no statistically significant differences among the different periods of treatment. Only IgG4 presented a negative correlation between its levels and clinical improvement during treatment. In total, 65% of untreated PCM patients showed reactivity against IgG4 when the Mexo antigen was used and this reactivity decreased over the course of treatment. There was a tendency towards decreasing antibody levels during treatment, but these antibody levels did not necessarily clear after the treatment was stopped. Mexo was useful for PCM diagnosis using total IgG; however, more studies are necessary before this antigen can be used in measuring the levels of total IgG and its subclasses for monitoring patients during treatment.

Profile of total IgG, IgG1, IgG2, IgG3 and IgG4 levels in sera of patients with paracoccidioidomycosis: treatment follow-up using Mexo and rPb27 as antigens in an ELISA

The levels of total of IgG, IgG1, IgG2, IgG3 and IgG4 were evaluated in 54 patients with chronic paracoccidioidomycosis (PCM) before, during and after treatment using an enzyme-linked immunosorbent assay with Mexo and recombinant Pb27 (rPb27) as the antigens. Mexo was effective in distinguishing PCM patients from individuals in the negative control group (NC) based on total IgG and rPb27 performed worse than Mexo when these two groups were compared. IgG1, IgG2, IgG3 and IgG4 could not be used to clearly distinguish PCM patients from those in the NC group using either antigen. There was no clear relationship between antibody levels and the period of treatment. The majority of patients presented with decreased antibody levels during treatment, with no statistically significant differences among the different periods of treatment. Only IgG4 presented a negative correlation between its levels and clinical improvement during treatment. In total, 65 percent of untreated PCM patients showed reactivity against IgG4 when the Mexo antigen was used and this reactivity decreased over the course of treatment. There was a tendency towards decreasing antibody levels during treatment, but these antibody levels did not necessarily clear after the treatment was stopped. Mexo was useful for PCM diagnosis using total IgG; however, more studies are necessary before this antigen can be used in measuring the levels of total IgG and its subclasses for monitoring patients during treatment.

Spleen cell proliferation during and after skin myiasis by human bot fly Dermatobia hominis.

Spleen cells from mice were examined at 5, 10, 15, 20 and 25 days post-infection (dpi) with Dermatobia hominis larva and at 5, 10, 15, 30 and 60 days post-larval emergence (dple). Cell proliferation in vitro assays were carried out with RPMI-1640 medium and larval secretory product (LSP) of D. hominis at 5, 10, 15, 20 and 25 days. When each group of mice was tested against each medium, significance was only seen for 25 dpi, with increasing order: LSP-10 d, -25 d, -5 d, -20 d, -15 d and RPMI. Significant results were also observed when each medium was tested against mice at each dpi or dple. Each dple group vs. each medium produced significant results only for 10 dple, with increasing order: LSP-5 d, -20 d, -25 d, -10 d, -15 d and RPMI. Comparative tests were also carried out between groups to refine certain observations. The LSPs were also analyzed using SDS-PAGE. The results prove that myiasis caused depletion of spleen cells, particularly under the effect of the LSP-10 and -15, but the cells tended to increase up to 60 dple. This in vitro assay may represent the real systemic immune response in the relationship LSP-D. hominis-host.

Spleen cell proliferation during and after skin myiasis by human bot fly Dermatobia hominis / Proliferação de células do baço durante e após miíase por Dermatobia hominis

Spleen cells from mice were examined at 5, 10, 15, 20 and 25 days post-infection (dpi) with Dermatobia hominis larva and at 5, 10, 15, 30 and 60 days post-larval emergence (dple). Cell proliferation in vitro assays were carried out with RPMI-1640 medium and larval secretory product (LSP) of D. hominis at 5, 10, 15, 20 and 25 days. When each group of mice was tested against each medium, significance was only seen for 25 dpi, with increasing order: LSP-10 d, -25 d, -5 d, -20 d, -15 d and RPMI. Significant results were also observed when each medium was tested against mice at each dpi or dple. Each dple group vs. each medium produced significant results only for 10 dple, with increasing order: LSP-5 d, -20 d, -25 d, -10 d, -15 d and RPMI. Comparative tests were also carried out between groups to refine certain observations. The LSPs were also analyzed using SDS-PAGE. The results prove that myiasis caused depletion of spleen cells, particularly under the effect of the LSP-10 and -15, but the cells tended to increase up to 60 dple. This in vitro assay may represent the real systemic immune response in the relationship LSP-D. hominis-host.

Células do baço de camundongos foram examinadas aos 5, 10, 20 e 25 dias pós-infecção (dpi) com Dermatobia hominis e examinadas aos 5, 10, 15, 30 e 60 dias pós-emergência da larva (dpel). As células foram cultivadas em meio RPMI-1640 contendo, ou não (controle), produtos de secreção das larvas (PSL) de D. hominis com idade de 5, 10, 15, 20 e 25 dias. Em cada grupo com cinco camundongos testados nos meios de cultura, o número de células foi significativo para 25 dpi, com crescente aumento na seguinte ordem: PSL-10 d, -25 d, -5 d, -20 d, -15 d e RPMI. Resultados significantes foram também observados nos testes entre cada meio contendo células tanto de camundongos dpi ou dpel. Em cada dpel grupo versus meio significância foi somente verificada para 10 dpel, na ordem crescente: PSL-5 d, -20 d, -25 d, -10 d, -15 d e RPMI. Testes comparativos foram também realizados entre grupos. O PSL foi analisado sob SDS-PAGE. Os resultados provam que a miíase causou depleção de células do baço, particularmente sob efeito do PSL-10 e -15, mas ocorreu normalidade do número de células aos 60 dpel. Este ensaio in vitro pode representar uma resposta imune sistêmica na relação PSL-D. hominis-hospedeiro.

Immunization with radioattenuated yeast cells of Paracoccidioides brasiliensis induces a long lasting protection in BALB/c mice.

Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a chronic systemic disease prevalent in Latin America. The aim of the present work was to evaluate the protection elicited by the immunization of BALB/c mice with radioattenuated yeast cells of P. brasiliensis. The immunization promoted a long lasting protection against highly infective yeast forms of P. brasiliensis. A 99.5% decrease in CFUs recovery was verified 90 days post challenge. At the same time the levels of IgG2a and IFN-gamma were high while a very low production of IL-10 and IL-5 was verified, suggesting that a Th1 pattern was dominant. This work shows the potential of radioattenuated yeast cells for the development of vaccines against fungi infections.