In silico and in vitro Evaluation of Mimetic Peptides as Potential Antigen Candidates for Prophylaxis of Leishmaniosis

Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all Leishmania species. To overcome this problem, we selected six potentially immunogenic peptides derived from Leishmania histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures.We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against L. braziliensis or L. infantum. Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected in vitro with L. braziliensis or L. infantum. The peptidemix generated the IFN-g, IL-12, IL-4 and TGF-b that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that themix of peptides derived fromhistone and parasitesmembranemolecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.Centro de Investigación y Desarrollo en Fermentaciones Industriale

PREVALENCE OF CHAGAS DISEASE AMONG BLOOD DONOR CANDIDATES IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL

Despite public health campaigns and epidemiological surveillance activities, Chagas disease remains a major health problem in Latin America. According to data from the World Health Organization, there are approximately 7-8 million people infected with Trypanosoma cruzi worldwide, a large percentage of which in Latin America. This study aims to examine the serological profile of blood donors in blood banks of Hemominas hematology center, in the town of Ituiutaba, Minas Gerais State, Brazil. The study sample consisted of 53,941 blood donors, which were grouped according to gender and age. Sample collections were performed from January 1991 to December 2011, and 277 donors (0.5%) were considered serologically ineligible due to Chagas disease. Analysis of data showed no significant difference between genders. As for age, the highest proportion of ineligible donors was from 40 to 49 years (30%), and there was a positive correlation between increasing age and the percentage of patients seropositive for Chagas disease. Therefore, adopting strategies that allow the safe identification of donors with positive serology for Chagas disease is essential to reduce or eliminate indeterminate serological results.A doença de Chagas, apesar das campanhas de saúde pública e das ações de vigilância epidemiológica, ainda constitui-se um sério problema de saúde na América Latina. De acordo com dados divulgados pela Organização Mundial de Saúde, existem cerca de 7 a 8 milhões de pessoas infectadas com Trypanosoma cruzi em todo o mundo, principalmente na América Latina. Este estudo tem por objetivo analisar o perfil sorológico de doadores de sangue dos bancos de sangue do Hemominas de Ituiutaba, Minas Gerais. Os doadores também foram separados de acordo com o sexo e a idade. A amostra do estudo foi composta por 53.941 doadores de sangue durante o período de janeiro de 2001 a dezembro de 2011. Duzentos e setenta e sete doações (0,5%) foram considerados sorologicamente inaptas para a doença de Chagas. Quanto à idade, a maior proporção de doadores impróprios foi de 40 a 49 anos (30%). Os dados não revelaram diferença significativa entre os sexos (p < 0,05). Houve correlação positiva entre o aumento da idade e o percentual de pacientes soropositivos para doença de Chagas. É imprescindível a adoção de estratégias que permitam a identificação segura de um doador com sorologia positiva para doença de Chagas, tentando assim minimizar ou eliminar resultados sorológicos indeterminados

In silico and in vitro Evaluation of Mimetic Peptides as Potential Antigen Candidates for Prophylaxis of Leishmaniosis

Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all Leishmania species. To overcome this problem, we selected six potentially immunogenic peptides derived from Leishmania histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures. We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against L. braziliensis or L. infantum. Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected in vitro with L. braziliensis or L. infantum. The peptide mix generated the IFN-γ, IL-12, IL-4 and TGF-β that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that the mix of peptides derived from histone and parasites membrane molecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.Fil: Guedes, Deborah Carbonera. Universidade Federal do Paraná; BrasilFil: Santiani, Manuel Hospinal. Universidade Federal do Paraná; BrasilFil: Carvalho, Joyce. Universidade Federal do Paraná; BrasilFil: Soccol, Carlos Ricardo. Universidade Federal do Paraná; BrasilFil: Minozzo, João Carlos. Universidade Federal do Paraná; Brasil. Secretaria de Saúde Do Estado Do Paraná; BrasilFil: Machado de Ávila, Ricardo Andrez. Universidade Do Extremo Sul Catarinense; BrasilFil: de Moura, Juliana Ferreira. Universidade Federal do Paraná; BrasilFil: Ramos, Eliezer Lucas Pires. Universidade Federal do Paraná; BrasilFil: Castro, Guillermo Raul. Laboratorio Max Planck de Biología Estructural, Química y Biofísica Molecular de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Chávez Olórtegi, Carlos. Universidade Federal de Minas Gerais; BrasilFil: Thomaz Soccol, Vanete. Universidade Federal do Paraná; Brasi