O Repositório digital do Instituto Butantan nasce com o objetivo de reunir, armazenar, preservar e dar visibilidade às publicações e ao conhecimento resultante das pesquisas realizadas pelo Instituto Butantan, no âmbito nacional e internacional, por meio da valorização e da disseminação de sua produção técnico-científica, acadêmica, educativa, cultural e administrativa.
7778 resultados
Submissões Recentes
Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Results of a randomized vaccine-controlled phase I ADAPTCOV trial in Brazil [2025]
Vaccine 2025 Apr; 52:126680
COVID-19 continues to be a health issue, mainly due to virus circulation and the emergence of new variants of concern and interest. This is a single-center, randomized, double-blind, active-controlled dose-escalating phase I clinical trial to evaluate the immunogenicity and safety of NDV-HXP-S (1 μg, 3 μg, and 10 μg), an inactivated COVID-19 vectored-vaccine virus using the Newcastle Disease Virus (NDV) expressing stabilized pre-fusion S protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthy SARS-CoV-2-naïve participants aged 18 to 59 years were randomized in a 3:3:3:1 ratio to receive two equal shots of 1 μg, 3 μg or 10 μg of NDVHXP-S formulations or placebo/CoronaVac intramuscular 28 days apart, respectively. Primary endpoints were solicited adverse events (AEs) determined within 7 days after each dose (safety) and proportion of seroconversion and geometric mean of 50 % neutralizing titer ratios against SARS-CoV-2 Wuhan-hu-1, Beta, and Gamma strains, measured on Day 42 after the first dose (immunogenicity). Follow-up occurred for 12 months for safety and immunogenicity evaluation. This study had substantial protocol amendments, the last one for early terminating the recruitment, as well as unblinding on Day 42. We included 311 subjects were in the safety population and 301 of them (97 %) received the second dose. More frequent solicited AEs were pain at the application site (<89 %), headache (<69 %), fatigue (<68 %), and myalgia (<61 %); most were classified as mild or moderate. There was no vaccine-related serious or grade-4 solicited AE. The proportion of participants reporting a vaccine-related unsolicited AE within 28 days after each dose ranged from 30 % to 33 % after the first dose and 14 % and 18 % after the second in NDVHXP-S, comparable to the control group. The 10 μg NDV-HXP-S formulation was the one that elicited the higher seroconversion values and neutralizing antibodies on Day 42 against SARS-CoV-2 strains. Up to 1-year follow-up, levels of bind antibodies remains about 2 log10 BAU/mL and no vaccine-related serious adverse event was
reported. Two NDV-HXP-S shots at 10 μg elicited the higher seroconversion and neutralizing antibody titers against the SARS-CoV-2. The vaccine also displayed a very favorable safety profile.
Papel do nódulo microglial na produção do inflamassoma e na manutenção do processo neuroinflamatório na infecção por SARS-CoV-2 em modelo experimental Golden Hamster [2024]
Com início em 2019 na cidade de Wuhan, na China central, a síndrome respiratória aguda causada pela infecção pelo novo coronavírus 2 (SARS-CoV-2) resultou na perda fatal de milhões de vidas humanas no planeta. Evidências científicas
comprovam que, mesmo após a recuperação da infecção por SARS-CoV-2 pacientes convalescentes, apresentam sintomas neurológicos graves que incluem hiposmia precoce, acidente vascular cerebral isquêmico, meningite, delírio e quedas. Tal fato, sugere, que às lesões teciduais conferidas pela infecção por SARS-CoV-2 podem estar associadas, às alterações crônicas ou permanentes no tecido nervoso. Entretanto, os mecanismos que regem estes efeitos não estão totalmente elucidados. Neste contexto, os mecanismos regulatórios e inflamatórios no tecido nervoso, são orquestrados por micróglias, incluindo a resposta imune às neuroinfecções virais. Dentre estes fatos, a formação de nódulo microglial é uma característica comum em doenças inflamatórias cerebrais e podem ser mediadas por linfócitos T, como encefalite viral e paraneoplásica, esclerose múltipla e encefalite de Rasmussen (ER). No entanto, seu papel ainda não foi totalmente compreendido. Assim, é possível presumir que parte dos mecanismos associados à intensificação ou perpetuação dos danos neurológicos sejam, de fato, associados à resposta imune destas célulasIsto posto, o presente estudo, teve como objetivo explanar o uso do modelo biológico Golden Hamster para elucidar o papel do nódulo microglial na ativação do inflamassoma e sua associação com a proteína Spike e elucidar o papel desta histoestrutura no processo neuroinflamatório. Para tal, foram avaliadas as lesões teciduais no tecido cerebral de Golden Hamsters infectados experimentalmente com partículas virais de SARS-CoV-2, sendo detectada a produção de ASC/inflamassoma em micróglias, bem como a associação da partícula viral com a produção de ASC nestas células in vivo. Achado este que projeta a descoberta de alvos moleculares importantes para novas terapias profiláticas e terapêuticas para esta doença.
Secreted factors of Aspergillus fumigatus cause lung epithelial barrier disruption: a study using an air-liquid interface cell culture model [2025]
Barros, Bianca Carla Silva Campitelli
Barros, Debora Tereza Lucas
Brock, Matthias
Toledo, Marcos Sergio
Suzuki, Erika
Ghaemmaghami, Amir M.
Med Mycol 2025 Mar; 63(3):myaf018
The effects of Aspergillus fumigatus-conditioned medium (AFCM) on the integrity of the Calu-3 cell lung epithelial barrier were investigated. AFCM led to a decrease in transepithelial electrical resistance and the disruption of the occludin network in the epithelial barrier. Preincubation with protease inhibitors reduced the effect of AFCM by ~ 90%, demonstrating the role of fungal proteases in epithelial barrier disruption. By mass spectrometry, we identified 494 unique proteins in AFCM, including 14 peptidases of different families. Together, these findings suggest that proteases secreted by A. fumigatus were able to modulate host epithelial barrier disruption in this fungal infection process.
School-based HPV vaccination program implementation in municipalities of the São Paulo State, Brazil, from 2015 to 2018 [2025]
Piorelli, Roberta de Oliveira
Sato, Helena Keiko
Araújo, Nubia Virgínia D’Ávilla Limeira de
Miyaji , Karina Takesaki
Sartori , Ana Marli Christovam
Cad. Saude Pública 2025 Feb; 41(2):e00127423
4vHPV vaccine was introduced into the Brazilian National Immunization Program in 2014, with vaccination at schools and healthcare facilities. Data on HPV vaccination program implementation in Brazil are scarce. This crosssectional, exploratory study aimed to get a better understanding of the HPV
vaccination actions and barriers to implement the school-based vaccination in municipalities of the São Paulo State, from 2015 to 2018, from the point of view of people who were responsible for conducting the actions. In November 2018, a questionnaire was sent to the state’s regional surveillance groups to
be answered by people responsible for the vaccination actions in the municipalities. The questionnaire consisted of six open questions on HPV vaccination actions taken by the municipalities, from 2015 to 2018, including whether the school-based vaccination had been implemented or not, a program description, the barriers to implement it, how the program was evaluated, and the municipality plans regarding HPV vaccination program in the following years. 233 (36.1%) of the 645 municipalities answered the questionnaire. Most of them implemented both education or vaccination actions at schools. Reported barriers were health human resources shortage, education staff concerns on vaccination within schools, and students’ and parents’ unfamiliarity with HPV vaccination. Raising awareness on HPV infection and prevention among students and parents, ensuring appropriate human resources, and building a partnership between the health and education sectors are critical to have a successful school-based program.
Species limits in Wiedomys (Cricetidae: Sigmodontinae) reinforce the South American São Francisco River as a biogeographic barrier [2025]
Lazar, Ana
Cunha-Filho, Carlos A.
Bezerra, Alexandra M.R.
Bonvicino, Cibele R.
Pessôa, Leila M.
Gonçalves, Pablo R.
Journal of Mammalogy 2025 Feb; 106(1):2-29
Red-nosed mice (genus Wiedomys) are restricted to the Brazilian Cerrado and Caatinga biomes, distributed along the São Francisco River (SFR). Until recently, Wiedomys was considered monotypic, but 2 species with poorly defined geographic and morphological limits have been recognized: W. cerradensis and W. pyrrhorhinos. Our study used morphological, phylogenetic, and cytogenetic analyses to review and detail species limits within the genus and test whether the SFR could be associated with divergence between lineages. This integrative approach indicated that the SFR delineates the geographic boundaries between species, with W. pyrrhorhinos on the right bank and W. cerradensis on the left bank. The species are reciprocally monophyletic and diverge in cranial size, nasal morphology, and facial pelage color pattern. Karyotypic differences between and within W. pyrrhorhinos and W. cerradensis were also detected, and new chromosome complements (2n = 62, FN = 96 and 2n = 62, FN = 88, respectively) were found. Divergence time (0.339 to 0.025 Ma) is concordant with the timing of diversification of other co-distributed vertebrate taxa, and close to a younger estimate for the formation of SFR’s recent lower course to the east coast. Therefore, our study considerably expands knowledge of the geographic range of the genus, diagnoses of species, karyotypic variability between and within species, and reinforces the role of SFR as an important vicariant barrier in northeastern Brazil.