EMED - Escola de Medicina
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/3649
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Item Cluster randomised trial to evaluate the effectiveness of a vaccine against cutaneous leishmaniasis in the Caratinga microregion, south-east Brazil.(2013) Mayrink, Wilson; Mendes, Alekson Mendonça; Paula, Jair Cecílio de; Siqueira, Liliane Maria Vidal; Marrocos, Simone de Resende; Dias, Edelberto Santos; Andrade, Hélida Monteiro de; Coelho, George Luiz Lins MachadoThe eco-epidemiological complexity of American cutaneous leishmaniasis (ACL) has made it difficult to devise an efficient strategy for management of the disease, and development of an effective vaccine remains the most promising approach. The objective of the study was to determine the reduction in incidence of ACL following intramuscular administration of two doses of a killed Leishmania (Leishmania) amazonensis vaccine.Item Field randomized trial to evaluate the efficacy of the Leish - Tec vaccine against canine visceral leishmaniasis in anendemic area of Brazil.(2016) Silva, Shara Regina; Feres, Ana Maria Leonardi Tibúrcio; Silva, João Carlos França da; Dias, Edelberto Santos; Michalsky, Érika Monteiro; Andrade, Hélida Monteiro de; Coelho, Eduardo Antônio Ferraz; Ribeiro, Gustavo Meirelles; Fernandes, Ana Paula Salles Moura; Coelho, George Luiz Lins MachadoBackground: A canine vaccine remains a promising approach for effective control of visceral leishmaniasis(VL), given its complex epidemiology in areas where zoonotic VL is prevalent. Leish-Tec®is a recombi-nant vaccine, based on the Leishmania A2 antigen, against canine VL (CVL). It is, since 2014, the singlecommercial vaccine licensed in Brazil. Here, Leish-Tec®efficacy was estimated through a randomizedfield trial (RFT), in a highly VL endemic area.Methods: The RFT was conducted from 2008 to 2010 in an endemic area of southeastern Brazil, presentinga CVL seroprevalence of 41.9%. Eight hundred forty-seven seronegative dogs were randomly selected toreceive Leish-Tec®(n = 429) or placebo (n = 418). Animals were followed up by clinical, serological, andparasitological exams for 18 months. The CVL incidence in both groups was compared through proportionanalysis.Results: A significant reduction in the number of cases of CVL was observed in the vaccine group, ascompared with the placebo group, whether efficacy was estimated according to parasitological results(71.4%; 95% CI: 34.9–87.3%; p = 0.001; risk ratio = 0.287), by adding results of xenodiagnosis and parasito-logical exams (58.1%; 95% CI: 26.0–76.3%; p = 0.002; risk ratio = 0.419). Among the animals that convertedto a positive anti-A2 serology, efficacy reached 80.8% (95% CI: 37.6–94.1%, p = 0.001; risk ratio = 0.192).Xenodiagnosis has detected a reduction of 46.6% (p = 0.05) in transmission to sand flies from vaccinatedanimals presenting anti-A2 positive serology.Conclusion: The Leish-Tec®vaccine proved significantly effective for prophylaxis of CVL, after naturalchallenge assured by transmission of Leishmania parasites, in a highly endemic area. Noteworthy, thisreport has unveiled the complexity of performing a RFT for anti-CVL vaccines in Brazil, which may behelpful for designing of future studies.Item Antibody responses induced by Leish-Tec®, an A2-basedvaccine for visceral leishmaniasis, in a heterogeneous caninepopulation.(2014) Testasicca, Miriam Conceição de Souza; Santos, Mariana Silva dos; Machado, Leopoldo Marques; Serufo, Ângela Vieira; Doro, Daniel; Avelar, Daniel Moreira de; Tibúrcio, Ana Maria Leonardi; Abrantes, Christiane de Freitas; Coelho, George Luiz Lins Machado; Grimaldi Junior, Gabriel; Gazzinelli, Ricardo Tostes; Fernandes, Ana Paula Salles MouraZoonotic visceral leishmaniasis (VL) is a widespread disease, and dogs are the main reser-voirs for human parasite transmission. Hence, development of an effective vaccine thatprevents disease and reduces the transmission of VL is required. As euthanasia of seropos-itive dogs is recommended in Brazil for VL epidemiological control, to include anti-VLcanine vaccines as a mass control measure it is necessary to characterize the humoralresponses induced by vaccination and if they interfere with the reactivity of vaccinateddogs in serological diagnostic tests. Leish-Tec®is an amastigote-specific A2 recombinantprotein vaccine against canine visceral leishmaniasis (CVL) that is commercially availablein Brazil. Here, we tested the immunogenicity of Leish-Tec®in a heterogeneous dog popula-tion by measuring A2-specific antibody responses. Healthy dogs (n = 140) of various breedswere allocated to two groups: one group received Leish-Tec®(n = 70), and the other groupreceived a placebo (n = 70). Anti-A2 or anti-Leishmania promastigote antigen (LPA) antibodylevels were measured by ELISA in serum samples collected before and after vaccination.An immunochromatographic test (DPP) based on the recombinant K28 antigen was alsoused for serodiagnosis of CVL. Vaccinated animals, except one, remained seronegative foranti-LPA total IgG and anti-K28 antibodies. Conversely, seropositivity for anti-A2 total IgGantibodies was found in 98% of animals after vaccination. This value decreased to 81.13% at6 months before rising again (98%), after the vaccination boost. Anti-A2 IgG2 and IgG1 titers.Item Vaccination of C57BL/10 mice against cutaneous leishmaniasis using killed promastigotes of different strains and species of Leishmania.(2002) Mayrink, Wilson; Santos, Gilmara Cristina dos; Toledo, Vicente de Paulo Coelho Peixoto de; Guimarães, Tânia Mara Pinto Dabés; Coelho, George Luiz Lins Machado; Genaro, Odair; Costa, Carlos Alberto daAntigenic extracts from five Leishmania stocks were used to vaccinate C57BL/10 mice. The Leishvacinand PH8 monovalent vaccine yielded the highest IFN-levels in the supernatants of spleen cell culture from vaccinated animals. Each single strain immunized group showed evidence of protective immunity six months after the challenge with promastigotes of Leishmania (Leishmania) amazonensis. No differences were detected between the vaccinated groups. It can be concluded that vaccines composed of single Leishmania stocks can provide protection to C57BL/10 mice against L. (L.) amazonensis infection.Item Making an anti-amastigote vaccine for visceral leishmaniasis : rational, update and perspectives.(2012) Fernandes, Ana Paula Salles Moura; Coelho, Eduardo Antônio Ferraz; Coelho, George Luiz Lins Machado; Grimaldi Junior, Gabriel; Gazzinelli, Ricardo TostesVisceral leishmaniasis is a major health problem in Latina America, as well as the Mediterranean region of Europe and Asia. We aimed to develop a vaccine against visceral leishmaniasis targeting the intracellular amastigotes, which is the parasite stage that persists throughout infections with Leishmania parasites. With this in mind, we identified an amastigote specific antigen (A2) that contains an immunogenic epitope for CD4+ T helper (Th) cells and multiple repetitive units encoding CD8+ cytotoxic T lymphocyte (CTL) epitopes. Vaccine formulations containing the recombinant A2 associated with saponin, alum and IL-12 or expressed by attenuated adenovirus were shown to be protective in mice, dogs and nonhuman-primates. We are currently identifying novel amastigote specific immunogenic proteins that could be aggregated to A2 to further improve the level of vaccineinduced cell-mediated immunity and protection against visceral leishmaniasis.