Background Venezuelan haemorrhagic fever (VHF), caused by Guanarito virus (GTOV), is a zoonotic disease endemic to the western plains of Venezuela. Despite decades of recognition, its epidemiology and clinical profile remain poorly characterised. Methodology We analysed individual level data from standardised case report forms submitted to the Venezuelan National Epidemiological Surveillance System between 2017 and 2024 for suspected VHF cases in Barinas, Apure, and Portuguesa. Demographic, clinical, and laboratory variables were examined to characterise temporal and geographical patterns and to define the clinical profile of VHF compared with endemic arboviral infections. Principal Findings Among 480 suspected cases, 72 (15.0%) were laboratory confirmed GTOV infections. Confirmed cases occurred predominantly in men engaged in agricultural or service related occupations, with the highest prevalence among individuals aged 46 to 90 years. A marked seasonal pattern was observed, with most cases occurring between September and January. The most frequently reported symptoms included headache, haemorrhage, sore throat, and diarrhoea. Compared with other endemic arboviral infections, GTOV was more strongly associated with headache, myalgia, sore throat, haemorrhage, and abdominal pain, delineating a distinct clinical phenotype relative to diseases caused by encephalitic alphaviruses, chikungunya virus, dengue virus, and Zika virus. The case fatality ratio among laboratory confirmed cases was 36.1% (95% CI: 25.1 to 48.3). GTOV infection was independently associated with mortality (adjusted relative risk [aRR] 3.66; 95% CI 2.28 to 5.87; p < 0.001), underscoring its substantial clinical severity. Conclusion GTOV remains endemically transmitted in western Venezuela, disproportionately affecting older men engaged in agricultural and service related occupations. Its seasonality and clinical phenotype, characterised by haemorrhage, sore throat, and gastrointestinal symptoms, highlight the need for clinical awareness and improved differential diagnosis, particularly in remote endemic settings with limited access to laboratory testing. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted using anonymised data derived from Venezuela National Epidemiological Surveillance System. In accordance with national regulatory requirements and institutional policies, the study protocol underwent ethical and technical review by the Ministry of People Power for Health and the Institute of Advanced Studies Dr. Arnoldo Gabaldon, and received formal approval on 17 October 2025 (G-200006221-5). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Due to data privacy considerations and a data use agreement with the Ministry of People Power for Health (Ministerio del Poder Popular para la Salud), Barinas, Venezuela, the data cannot be made publicly available. Data may be available upon reasonable request to the Ministry of People Power for Health, subject to approval and in accordance with national and institutional regulations governing the use of surveillance data.

Infants represent a vulnerable population for severe outcomes from infectious diseases. For dengue virus, maternal antibodies can cause severe disease in infants aged 5-12 months through antibody-dependent enhancement, but the role of maternal immunity in neonates aged 0-30 days has not been quantified. Our study leverages the re-emerging setting of Brazil, where the proportion of mothers with anti-dengue antibodies varies across space and time. Infant dengue burden has risen 11-fold from 2000-2024, in line with expansion in the general population. We fit mechanistic models to infant dengue and severe dengue cases reported through surveillance to disentangle the competing roles of maternal immunity, transmission, and age on the risk of dengue and severe dengue in infants across the first year of life. We observed peaks in severe dengue risk in neonates and at 7-8 months of age. These two peaks were explained by competing mechanisms. Infants born to seropositive mothers had lower overall risk of dengue, but increased risk of severe disease from 5-12 months, than those born to seronegative mothers. As dengue incidence increases, and vaccination becomes available, maternal antibodies may decrease infant burden but increase the risk of severe disease.

Dengue continues to pose a significant global health threat. However, the development of a safe and effective tetravalent vaccine is impeded by complex serotype-specific and cross-reactive immune responses. This review assesses licensed and advanced dengue vaccines, emphasizing serostatus-dependent safety, serotype imbalance, and the durability of protection. It also critically evaluates immunological correlates of protection and addresses remaining obstacles, such as vector-mediated immune modulation and orthoflavivirus cross-reactivity, to guide future dengue vaccine strategies.

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 ).

The vast diversity of the virosphere underscores the need for rapid, adaptable vaccine development infrastructures. Arthropod-borne zoonotic alphaviruses, in particular, continue to pose substantial threats to human and animal health. We present a fast, multitarget vaccine design pipeline integrating machine learning-based epitope prediction, protein modeling, and docking to prioritize viral peptides by immunogenicity, allele coverage, solubility, and stability. T cell epitopes were validated using peptide microarrays and molecular dynamics simulations, confirming receptor binding accuracy. Flow cytometry of murine and human peripheral blood mononuclear cells demonstrated robust T cell activation and cytokine secretion (IFN-γ, TNF-α, or IL-2), dependent on species and HLA allele. Final candidates were selected by composite immunogenicity scores. While this study primarily validates the T cell-specific arm of our predictive pipeline, complementary B cell epitope analyses are ongoing. Our findings support the development of broadly protective pan-alphaviral vaccines and the establishment of efficient, tunable processes for global vaccine development.

Dengue causes over 390 million annual infections globally. Qdenga (TAK-003), the only widely available dengue vaccine, has an incompletely defined immunological profile. We performed longitudinal immunological profiling of 110 adults from a dengue-endemic region, including older adults (≥65 years), to assess the effects of immune imprinting and vaccine design on humoral and cellular immunity. Qdenga elicited B and T cell activation across groups but generated serostatus-dependent, serotype-skewed antibody responses. Only 8% of DENV-naïve individuals developed tetravalent neutralizing responses, whereas one-third responded to a single serotype, predominantly DENV-2, the vaccine backbone. DENV-exposed individuals mounted broader responses shaped by preexisting immunity, yet DENV-4 neutralization remained consistently poor. Neutralizing antibody titers plateaued after the first dose, with no increase following the second. These findings clarify why balanced tetravalent immunity is rarely achieved with Qdenga and demonstrate that both immune imprinting and vaccine backbone limit the breadth and magnitude of the responses. This has important implications for deployment, long-term protection in naive populations, and DENV-4-targeted boosters.

Dengue remains a major global health threat, with over 390 million annual infections. The development of safe, effective, and broadly protective vaccines has been hindered by the need for tetravalent coverage and the risk of antibody-dependent enhancement (ADE). Qdenga (TAK-003) is the only dengue vaccine currently widely available globally, yet its immunological profile remains incompletely defined. Here, we characterized humoral and cellular responses, assessing the impact of the vaccine backbone and immune imprinting on vaccine-induced immunity. We conducted a longitudinal immunological study in 110 adults from a dengue-endemic region, stratified by baseline DENV serostatus, sex, and age, including older adults (≥65 years), a population excluded from efficacy trials. Plasma and PBMCs were collected before and up to five months after Qdenga vaccination to assess neutralizing antibody titers, B cell dynamics, and virus-specific T cell responses. Although Qdenga elicited B and T cell activation and memory formation across groups, our findings revealed serostatus-dependent and serotype-skewed humoral immunity. Only 8% of DENV-naïve individuals developed tetravalent responses, while one-third responded to a single serotype, almost exclusively DENV-2, the vaccine backbone. In contrast, DENV-previously exposed individuals mounted broader responses shaped by baseline serotype-specific immunity, yet neutralization against DENV-4 remained uniformly poor. Neutralizing antibody titers plateaued after the first vaccination, with no substantial increase following the second dose. These findings clarify why balanced tetravalent immunity is rarely achieved with Qdenga and demonstrate that both immune imprinting and vaccine backbone skewing limit the breadth and magnitude of the responses. This has important implications for deployment strategies, long-term protection in DENV-naïve populations, and the need for booster strategies focusing on tetravalent coverage, especially for DENV-4.

Arboviruses are mosquito-borne viruses of major public health importance, particularly in tropical and subtropical regions. In Paraguay, dengue (DENV) and chikungunya (CHIKV) viruses are among the most epidemiologically relevant; however, studies integrating mosquito and arbovirus surveillance remain scarce. This study aimed to characterize mosquito assemblage composition across different ecological settings and investigate arbovirus circulation in field-collected mosquitoes. A total of 4,595 mosquitoes (609 pools) were collected between 2013 and 2024 from urban, rural, and Atlantic Forest environments in Paraguay. Twenty-six mosquito species were identified, with Culex quinquefasciatus (55.3%) as the most abundant, followed by Aedes (Ochlerotatus) scapularis (13.3%). Aedes aegypti (7.3%) was mainly associated with urban areas. Diversity analyses showed higher alpha diversity and greater gamma diversity in the Atlantic Forest and lower values in rural areas, whereas high beta diversity indicated substantial species turnover among locations. Molecular screening by real-time RT-PCR detected no evidence of West Nile, Saint Louis encephalitis, Venezuelan equine encephalitis, Mayaro, yellow fever, Zika, or Oropouche viruses. In contrast, A. aegypti pools tested positive for DENV (n=3; 2021 and 2023) and CHIKV (n=3; 2023). Phylogenetic reconstruction confirmed the circulation of DENV-4 Genotype II (lineage B.1.1), DENV-2 Genotype II (F.1.1.2), and CHIKV East/Central/South African (ECSA) lineages in Paraguay, all closely related to human outbreak-associated sequences. These findings provide the first molecular evidence of arbovirus infection in field-collected mosquitoes in Paraguay and emphasize the importance of integrated entomological and viral surveillance.

Oropouche virus (OROV) spread across the Americas in 2024, yet Panama’s Darién migration corridor saw no outbreak until nearly a year after Brazil’s January 2024 peak, raising two hypotheses: cryptic circulation masked by diagnostic gaps, or recent introduction under permissive climatic conditions. Here we resolve this paradox using integrated clinical, genomic, and climate-informed surveillance. Among 1,040 individuals tested, 43% were OROV-positive and showed a clinical signature distinct from co-circulating arboviruses, including headache more frequent than in dengue (RR 2.38, 95% CI 1.74-3.24). The household secondary attack rate was 56%, and waste burning independently predicted infection. Phylogeographic reconstruction identified a single recent introduction in October 2024 with no evidence of adaptive evolution, excluding prolonged cryptic persistence. Climate-informed models indicate broad outbreak susceptibility across Panama, with Bocas del Toro and Los Santos as the next highest-risk provinces. These findings identify a Central American foothold for OROV with potential for further northward spread.

Pneumonia and diarrhea are the leading causes of death in children under 5 globally, worsened by viral infections. This study investigates viral agents in children ≤ 3 years with respiratory illness and diarrhea in Metropolitan Region of São Paulo, Brazil, during spring 2021. Twenty paired samples (oropharyngeal swab and feces) were tested using in-house qPCR for HBoV and HAdV, RT-qPCR for RVA, EV, PeV-A, and NoV, and a commercial RT-qPCR kit for SARS-CoV-2, Flu A/B, and RSV. HAstV was detected with conventional nested (RT)-PCR. Positive samples were sequenced for molecular characterization and phylogenetic analysis. Seven viruses were identified: HBoV, NoV, HAdV, PeV-A, EV, RSV, and Flu A. HBoV and NoV were detected in 75% of cases, with co-infection in 65% of patients, indicating their involvement in the gastro-respiratory illness. Genotyping of HBoV (HBoV-1), NoV (GII.4_Sydney[P16], GII.2[P16], and GII.4_Sydney[P31]), EV (Coxsackievirus A6), HAdV (species C, type 6), and PeV-A (genotype 1) showed local virus diversity. Phylogenetic analysis indicated no ongoing community outbreak, with distinct clusters observed. The findings highlight the overlap of respiratory and enteric diseases, revealing local viral diversity and high exposure to enteric viruses. This underscores the challenges in differential diagnosis and the need for syndromic surveillance.

We detected yellow fever virus in Haemagogus mosquitoes collected in 2022 in an Amazon rainforest bordering Manaus, Brazil. The viral genome sequence occupied a basal position within the South American I genotype 1E lineage. Our findings reinforce the Amazon Basin as a source for yellow fever virus re-emergence.

Vaccines are essential for the prevention and control of several diseases, and monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined in terms of the intensity and medium to long-term duration of protective immunity, which may indicate the need for booster doses and could support decisions in public health. The study aims to evaluate the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescents aged 3 to 17 years old in Brazil. Participants were invited to the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. They underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, which included measurements of weight, blood pressure, temperature, and pulse rate. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and at 1, 3, and 6 months after the second dose. These samples were followed up using a virtual platform to monitor post-vaccination reactions and symptoms of COVID-19. The SARS-CoV-2 genome from swab samples of COVID-19 positive individuals was sequenced using NGS. Total antibodies were measured by ELISA, and neutralizing antibodies to the B.1 lineage and Omicron variant (BA.1) were quantified by PRNT and VNT assays. The cellular immune response was evaluated by flow cytometry through the quantification of systemic soluble immune mediators. The follow-up of 640 participants showed that CoronaVac was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to the B.1 lineage and Omicron variant. Additionally, a robust cellular immune response was observed, characterized by a wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient, except for seven serious adverse events reported on VigiMed. The results indicate a robust and sustained immune response induced by CoronaVac in children and adolescents for up to six months, providing evidence to support the safety and immunogenicity of this effective immunizer.

Background Chikungunya outbreaks have been reported in Brazil since 2014. Adolescents are a sensitive population who would benefit from a prophylactic vaccine. This study assessed the immunogenicity and safety of the vaccine VLA1553 in adolescents in Brazil. With an overall trial duration of 12 months, we now report data on safety and immunogenicity over a period of 28 days after vaccination. Methods In this double-blind, randomised, placebo-controlled phase 3 trial, adolescents aged 12 to <18 years were recruited. The trial was performed at ten trial sites across Brazil. Eligible participants were generally healthy. The main exclusion criteria comprised immune-mediated or chronic arthritis or arthralgia, a known or suspected defect of the immune system, or any live vaccine received within the 4 weeks before trial vaccination. Randomisation was stratified by baseline serostatus in a 2:1 ratio to receive VLA1553 (at a dose of 1 x 10(4) TCID50 per 05 mL [ie, 50% tissue culture infectious dose]) or placebo. VLA1553 or placebo was administered intramuscularly as a single-dose immunisation on day 1. The primary endpoint was the proportion of baseline seronegative participants with chikungunya virus neutralising antibody levels of 150 or more in mu PRNT50 (a micro plaque reduction neutralisation test), which was considered a surrogate of protection. The safety analysis included all participants receiving a trial vaccination. Immunogenicity analyses were performed in a subset. The trial is registered with ClinicalTrials.gov, NCT04650399. Findings Between Feb 14, 2022, and March 14, 2023, 754 participants received a trial vaccination (502 received VLA1553 and 252 received placebo) with a per-protocol population of 351 participants for immunogenicity analyses (303 in the VLA1553 group and 48 in the placebo group). In participants who were seronegative at baseline, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 247 of 250 (988%, 95% CI 965-998) participants 28 days after vaccination. In seropositive participants, the baseline seroprotection rate of 962% increased to 100% after vaccination with VLA1553. Most (365 [93%] of 393) adverse events were of mild or moderate intensity, VLA1553 was generally well tolerated. When compared with placebo, participants exposed to VLA1553 had a significantly higher frequency of related adverse events (351 [699%] of 502 vs 121 [480%] of 252; p<00001), mostly headache, myalgia, fatigue, and fever. Among four reported serious adverse events (three in the VLA1553 group and one in the placebo group), one was classified as possibly related to VLA1553: a high-grade fever. Among 20 adverse events of special interest (ie, symptoms suggesting chikungunya-like disease), 16 were classified as related to trial vaccination (15 in the VLA1553 group and one in the placebo group), with severe symptoms reported in four participants (fever, headache, or arthralgia). 17 adverse events of special interest resolved within 1 week. Among 85 participants with arthralgia (68 in the VLA1553 group and 17 in the placebo group), eight adolescents had short-lived (range 1-5 days), mostly mild recurring episodes (seven in the VLA1553 group and one in the placebo group). The median duration of arthralgia was 1 day (range 1-5 days). The frequency of injection site adverse events for VLA1553 was higher than in the placebo group (161 [32%] vs 62 [25%]), but rarely severe (two [<1%] in the VLA1553 group and one [<1%] in the placebo group). After administration of VLA1553, there was a significantly lower frequency of solicited adverse events in participants who were seropositive at baseline compared with those who were seronegative (53% vs 74%; p<00001) including headache, fatigue, fever, and arthralgia. Interpretation VLA1553 was generally safe and induced seroprotective titres in almost all vaccinated adolescents with favourable safety data in adolescents who were seropositive at baseline. The data support the use of VLA1553 for the prevention of disease caused by the chikungunya virus among adolescents and in endemic areas.

BACKGROUND:The 2024 Oropouche virus (OROV) outbreak in Brazil raised public health concerns due to its unprecedented rapid spread, high incidence, and potential neurological complications. OROV symptoms overlap with locally endemic arbovirus diseases, like dengue virus (DENV), complicating diagnosis. The study aimed to compare clinical, laboratory, and immunological profiles in OROV and DENV cases, crucial for improving diagnosis and management. METHODS:This study analyzed 51 OROV and 78 of DENV cases consecutively enrolled in Manaus, Amazonas, Brazil, and monitored for 28 days. OROV diagnosis was performed by real-time PCR (RT-PCR) using serum and urine samples. OROV RT-PCR positive samples were genotyped. A paired Plaque Reduction Neutralization Test (PRNT) was conducted on samples collected at D1 and D28. Patients with a ≥ 4-fold increase in neutralizing antibody titer between D1 and D28 were considered OROV-positive. Clinical manifestations, hematology, biochemistry, and cytokine profiles were analyzed. Statistical analysis included comparison between OROV and DENV patients. RESULTS:Genome sequencing of OROV isolates confirmed presence of a previously reported novel reassortment event, consistent with ongoing localized transmission. Urine RT-PCR demonstrated low positivity compared to serum samples. The paired PRNT increased sensitivity in 45%. Clinically, OROV infection was associated with significantly higher frequencies of severe headache, myalgia, arthralgia, and rash compared to DENV infection (p < 0.001). Elevated alanine aminotransferase (ALT) levels were also observed in OROV patients (p < 0.001). Immunologically, OROV infection induced significantly increased levels of acute-phase CCL11 (eotaxin), CXCL10, IFN-γ, IL-1RA, and IL-10, which declined by day 28, while IL-5 increased during recovery. In contrast, DENV patients exhibited elevated levels of CCL2, G-CSF, and CCL3 in recovery phase. CONCLUSION:OROV symptoms overlap with DENV underscores the need for syndromic diagnostic approach in endemic regions. Continued genomic surveillance and expanded clinical studies are vital to assess long-term consequences. Given OROV's expanding geographic range, targeted public health measures are essential to mitigate future outbreaks and better understand its pathophysiology.

The aim of this study was to investigate the influence of HLA-A, -B and -C polymorphisms on the clinical course of SARS-CoV-2 infection and on the progression of COVID-19 in a population from southeastern Brazil. This study included 478 unvaccinated individuals. Of these, 369 were hospitalised with critical/severe (n = 309) or moderate/mild (n = 60) symptoms, and 109 were asymptomatic. The control group consisted of 150 volunteer bone marrow donors, recruited in the pre-pandemic period. The HLA-B*15 allele group (adjusted p value < 0.001) was associated with a protective factor against symptomatic infection. Investigating the effects of the distribution of HLA alleles on susceptibility and resistance to SARS-CoV-2 may provide a better understanding of the clinical course of infection in different geographical regions.

In 1923, H.R. Carter published a seminal treatise on the possibility of yellow fever virus spreading to the Asia Pacific region, where large numbers of susceptible people were at risk of infection. This paper marks the 100th anniversary of that publication, and posits that, despite many public health advances, global trends increase the likelihood of yellow fever virus geographic spread. Potential reasons for the failure of the virus to spread are discussed.

BACKGROUND:CoronaVac, an inactivated COVID-19 vaccine, underwent evaluation for its efficacy and safety during the PROFISCOV study conducted in Brazil. METHODS:Between July 21, 2020, and July 29, 2021, 13,166 participants provided informed consent, with 12,688 randomized for the trial. Participants were allocated between vaccine and placebo arms (1:1) and monitored for symptomatic COVID-19 cases, severity of disease, and adverse reactions after two doses given 14 days apart. FINDINGS:The primary efficacy analysis revealed a vaccine efficacy of 50⸱4 % (95 % confidence interval [CI], 35·3 % to 62·0 %; p = 0·0049) in preventing symptomatic COVID-19, leading to the issuance of Emergency Use Authorization for CoronaVac in January 2021. Upon completion of follow-up, vaccine efficacy was 44⸱6 % [95 % CI, 34·9 % to 52·8 %; p = 0·0023] in preventing COVID-19 and 82⸱1 % (95 % CI, 64·9 % to 90·9 %; p < 0·0001) in preventing severe COVID-19. Safety data indicated that adverse reactions were more frequent in the vaccine arm, primarily mild to moderate, with pain at the injection site and headache being the most common. INTERPRETATION:CoronaVac demonstrated moderate efficacy in preventing symptomatic COVID-19 and high efficacy against severe disease. While reactions were slightly more common in the vaccine group, they were generally mild and manageable. FUNDING:Fundação Butantan, Instituto Butantan, and São Paulo Research Foundation (FAPESP; Grants 2020/10127-1 and 2020/06409-1).