Instituto Butantan (in modern Portuguese, Instituto Butantã, pronounced [ĩʃtʃiˈtutu butɐ̃ˈtɐ̃]) is a Brazilian biologic research center located in Butantã, in the western part of the city of São Paulo, Brazil. Instituto Butantan is a public institution affiliated with the São Paulo State Secretariat of Health and considered one of the major scientific centers in the world. Butantan is the largest immunobiologicals and biopharmaceuticals producer in Latin America (and one of the largest in the world). It is world-renowned for its collection of venomous snakes, as well as those of venomous lizards, spiders, insects and scorpions. By extracting the reptiles' and insects' venoms, the Institute develops antivenoms and medicines against many diseases, which include tuberculosis, rabies, tetanus and diphtheria.
In individuals with prior dengue virus (DENV) exposure, subsequent heterotypic infection can increase the risk of severe disease. A single-dose dengue vaccine that protects against the four DENV serotypes across a wide age range and regardless of DENV serostatus is needed. Here we report the long-term safety and efficacy of Butantan dengue vaccine (Butantan-DV), a live, attenuated, tetravalent dengue vaccine, among participants ages 2-59 who were randomized 2:1 in a double-blind, placebo-controlled, phase 3 trial in Brazil. A primary objective was to evaluate vaccine efficacy (VE) against reverse transcription-PCR-positive symptomatic dengue 28 days after vaccination because of any DENV serotype, regardless of serostatus. Prespecified secondary endpoints included VE by serotype, by serostatus and against severe dengue or dengue with warning signs (combined). The primary and secondary objectives were met if the lower bound of the two-sided 95% confidence interval (CI) for VE was above 25%. Between 2016 and 2019, 16,235 participants received Butantan-DV (n = 10,259) or placebo (n = 5,976). The trial met the primary and secondary objectives. During the 5 years of follow-up, between 2016 and 2024, overall VE (95% CI) was 65.0% (57.8-71.0%). Secondary VE endpoints (95% CI) were 77.1% (67.6-83.9%) in dengue-experienced participants, 58.9% (48.0-67.6%) in dengue-naive participants, 73.0% (64.3-79.7%) against DENV-1 and 55.7% (42.3-66.1%) against DENV-2. Cases of DENV-3 or DENV-4 were not observed. VE (95% CI) against dengue with warning signs or severe dengue (secondary endpoint) was 80.5% (50.8-92.4%). The most commonly reported solicited systemic adverse event (AE) was headache (36.7% of vaccine recipients and 31.1% of placebo recipients), most of which were grade 1. The proportions of participants with unsolicited vaccine-related AEs (including serious AEs) were comparable between intervention groups. A single dose of Butantan-DV was efficacious against symptomatic virologically confirmed dengue because of DENV-1 or DENV-2, regardless of dengue serostatus at baseline, with no safety concerns observed during the 5-year follow-up (ClinicalTrials.gov: NCT02406729 ).
Background/Objectives: Schistosomiasis is a neglected tropical disease affecting >200 million people worldwide. Praziquantel is the sole recommended drug against Schistosoma mansoni; however, it lacks activity against juvenile forms and cannot prevent reinfection. Thus, there is an urgent need to identify novel therapeutic targets. Long noncoding RNAs (lncRNAs) are known to regulate various biological processes in S. mansoni, including parasite pairing and fertility; therefore, screening for novel lncRNAs could reveal new potential targets. Methods: We compiled all publicly available RNA-seq data from the Sequence Read Archive (SRA) and performed a hierarchical transcriptome assembly using the multi-sample assembler Ryūtō, combined with version 10 of the S. mansoni genome. We applied HOMER for peak-calling and identification of histone marks and used weighted gene co-expression network analysis (WGCNA) to infer putative functions of lncRNAs in sexual dimorphism. Results: Using a robust pipeline, we identified 10,170 novel lncRNA genes comprising 16,990 novel lncRNA transcripts, including 8783 intergenic, 7918 antisense, and 289 intronic lncRNA transcripts. Most (78.7%) have histone regulatory marks (H3K4me3, H3K27me3, H3K27ac, or H4K20me1) near their transcription start sites, indicating potential expression regulation. Comparing male and female samples, we identified 1991 differentially expressed genes (FDR < 5%, |log2FC| ≥ 1.5), including 296 known lncRNAs and 339 novel lncRNAs. WGCNA identified hub lncRNAs within co-expression modules, and Gene Ontology enrichment analyses (FDR ≤ 5%) suggest that these lncRNAs are involved in cell differentiation and morphogenesis pathways. Conclusions: We provide a comprehensive catalog of S. mansoni lncRNAs. These findings offer opportunities to discover potential new therapeutic targets, advancing the future development of anti-schistosome therapies.
BACKGROUND:Dengue is caused by infection with 1 of 4 dengue virus (DENV) serotypes (DENV-1 to DENV-4). V181 and Butantan-Dengue Vaccine (Butantan-DV) are independently developed, single-dose, quadrivalent dengue vaccines based on the same attenuated parental strains. METHODS:In this randomized, double-blind, active comparator-controlled, multisite, phase 2 trial, we compared the safety and immunogenicity of V181 and Butantan-DV in healthy adults in Brazil. The primary immunogenicity objectives were to compare vaccine-induced neutralizing antibody geometric mean titers (GMTs) and seroconversion rates for DENV-1 to DENV-4 at day 28 postvaccination. The primary and secondary safety objectives, respectively, were to assess vaccine-related serious adverse events and the proportion of participants experiencing solicited adverse events through day 28 postvaccination. RESULTS:Overall, 1364 participants were assigned (1:1) to receive V181 (n = 682) or Butantan-DV (n = 682). At day 28 postvaccination, V181 induced a noninferior immune response to Butantan-DV for DENV-1 and DENV-2 but not DENV-3 and DENV-4, as measured using GMT ratios. Noninferiority was established for all DENV serotypes based on seroconversion rates. Most participants developed a trivalent or tetravalent neutralizing antibody response. Vaccine viremia was detected for each DENV serotype. V181 and Butantan-DV were generally well tolerated. CONCLUSIONS:V181 was immunogenic in adults, and while immunogenicity was noninferior to Butantan-DV for DENV-1 and DENV-2, seroconversion rates were noninferior for DENV-1 to DENV-4. The safety profile of V181 is comparable to that of Butantan-DV and supports its continued evaluation as a single-dose quadrivalent vaccine for dengue prevention. CLINICAL TRIALS REGISTRATION:NCT05710224.
Megalomyrmex ant species have a rich natural history that provides an interesting backdrop to understanding how venom has been shaped by evolution. However, like many other species in the tribe Solenopsidini, alkaloid investigations have dominated, limiting our understanding of the diversity of venom components. Here we use transcriptomics to qualify and quantify the proteins and peptides within Megalomyrmex milenae, a species of ant native to the Panamanian rainforest along the Panama Canal. RNA transcripts associated with and over-expressed in the venom gland allow the description of putative toxins and other significant protein components of the venom cocktail. Among other constituents, we find signatures for pore-forming toxins, neurotoxins, carbohydrate-digesting enzymes, proteins which potentially enhance trail pheromone efficacy, and peptides implicated in antimicrobial activity. This work greatly enhances our understanding of Megalomyrmex venoms, showing a multifaceted functional venom profile similar to other ant species. However, proteomic and functional assays are needed to clarify the venom functions hypothesized in this work.
Purple martins (Progne subis) are migratory aerial insectivores that have experienced a 37% population decline over the past five decades. One hypothesized cause for this decline is exposure to contaminants at their non-breeding grounds. However, non-breeding grounds of purple martins extend over 35 degrees latitude in South America, likely resulting in different contaminant exposure scenarios. In this study, we compare total mercury (THg) content in feathers from 247 purple martins from two roosts in Brazil: one in the Amazon Basin and another in the southeast region. We hypothesized that birds in the Amazon region would exhibit the highest feather THg content due to the combined influence of anthropogenic activities and the region's geological features. However, mean THg feather contents were significantly higher in the southeast (3.2 ± 1.6 μg g-1) than in the Amazon Basin (1.77 ± 0.81 μg g-1), likely driven by local and regional environmental factors, including industrialization and historical land-use change. Our findings highlight the importance of understanding how the non-breeding range of migratory species may influence their contaminant exposure. This information will assist in the development of conservation strategies tailored to the unique environmental conditions migratory species are exposed to throughout their annual cycles.
