Search Results (84)

Yellow fever (YF) is an acute hemorrhagic zoonotic disease that causes severe liver damage, renal failure, and hemorrhagic shock. No antiviral treatment is available; thus, vaccination is a critical preventive measure. Although the World Health Organization (WHO) revised the guidelines regarding the need for booster vaccination for YF with the rationale that a single vaccination provides sufficient long-term immunogenicity, no studies have evaluated long-term immunity in Japanese adults who received a single dose of YF vaccine. This study evaluated the long-term persistence of immunogenicity in Japanese adults vaccinated with the YF vaccine. This observational study enrolled Japanese adults who received a single YF vaccination >5 years previously. Blood samples were collected after confirming eligibility for the study. The serum levels of anti-yellow fever virus (YFV)-neutralizing antibodies were measured using the 50% plaque reduction neutralization test (PRNT₅₀). The 65 participants comprised 35 males and 30 females, with a median age at vaccination of 34 years. The time between YF vaccination and registration was between 5 and 26 years. All participants remained seropositive even after a long time. Statistical analysis showed no correlation between the time elapsed since YF vaccination and PRNT₅₀. Our results indicate that a single dose of YF vaccine provides adequate long-term immunity in Japanese adults and that booster vaccinations are not routinely required. These findings strongly aid in the development of travel medicine guidelines and the optimization of vaccination strategies by reducing the usage of medical resources and simplifying the health requirements for travelers. Full article

Background/Objective: Yellow fever (YF) is an acute infectious disease caused by the yellow fever virus which is transmitted by mosquitoes. Neotropical primates are susceptible to infection, which is often presented as epizootic outbreaks. The aim was to evaluate and characterize the immune response against YF in different species of neotropical primates from the Belo Horizonte Zoo. Methods: Vaccine 17DD was administered to 24 neotropical primates, with a single subcutaneous dose. Clinical exams, RNAemia, and detection of IgG and neutralizing antibodies against YFV were performed. In addition, an ethogram was performed to assess clinical changes and animal welfare. Results: At 4 days post-vaccination, RNAemia was detected in nine animals. There was seroconversion and persistence of immune response in Alouatta guariba clamitans, Sapajus xanthosternos, Saguinus imperator and Aotus infulatus. However, the vaccine was not immunogenic for Lagothrix cana. In Pithecia irrorata seroconversion did not persist long term, while the Ateles sp. had a transient immune response. No significant clinical manifestations were observed in any of the vaccinated animals. Conclusions: This study demonstrated a safe, immunogenic and persistent immune response induced by the attenuated 17DD vaccine strain in A. guariba clamitans, S. xanthosternos, S. imperator, and A. infulatus. Full article

Flaviviruses are a group of viruses transmitted mainly by mosquitoes and ticks, causing severe diseases in humans. Examples include dengue, Zika, West Nile virus, and yellow fever. They primarily affect individuals in tropical and subtropical regions, causing public health problems such as epidemic outbreaks and significant economic burdens due to hospitalizations and treatments. They share antigens, leading to cross-reactivity where antibodies generated against one flavivirus can react with others, complicating the accurate diagnosis of individual infections and making the development of treatments or vaccines more challenging. The role of T cells in the immune response to flaviviruses is a complex topic debated by scientists. On one hand, T cells help control infection by eliminating infected cells and protecting against disease. However, there is evidence that an excessive or dysregulated T cell response can cause tissue damage and worsen the disease, as seen in severe dengue cases. This duality underscores the complexity of the immune response to flavivirus infections, posing a significant challenge for researchers. Gaining a deeper understanding of the immune response at the cellular level, particularly the role of T follicular helper cells, can reveal new avenues of investigation that could lead to novel strategies for disease management. This review explores the dynamics of T cell responses, focusing on circulatory T follicular helper cells (cT_FH), to enhance our understanding of flavivirus immunity and inform future interventions. Full article

Yellow fever (YF) causes severe morbidity and mortality in Africa and South America. It is an arthropod-borne viral disease endemic to tropical regions of Africa and South America. Yellow fever virus (YFV) is transmitted by mosquitoes and frequently affects both non-human primates (NHPs) and humans. Neotropical primates (NTPs) are generally more severely afflicted by YFV than African primates. Asian primates appear not to be susceptible to this disease. Susceptibility varies among NTP species: asymptomatic infections are described in some NTP species, whereas severe epizootic mortality events are described in others. The genus Alouatta (howler monkeys) is considered to be the most susceptible among the NTPs. Epizootic events resulting in the death of thousands of NTPs have been recorded in recent history. As a result, YFV poses a threat to the survival of some NTP species. In most cases, NTPs are found dead without showing prior clinical signs. In cases where clinical signs are observed, they are mostly non-specific. Due to their high susceptibility, epizootic events in NTPs are used as epidemiological predictors for human YF outbreaks. YFV infection may be diagnosed by means of virus isolation, reverse transcription polymerase chain reaction, serology, histopathology, or immunohistochemistry. Animals that survive the disease develop neutralizing antibodies to YFV. Currently, no specific treatment is available. Sustained YF control strategies must rely on surveillance and accurate diagnostics to allow for early detection of outbreaks and rapid implementation of control measures. Prophylaxis should be based on a One Health perspective that recognizes the intricate interplay between human health, primate health, and the environment. Vaccines for YF are available, with the human 17DD vaccine effectively preventing disease in primates. However, mitigation strategies continue to rely more and more on vector control, preferably using eco-friendly methods. Climate change and human activities, and their impact on local ecology, are assumed to increase the risk of YF transmission in the next decades. Full article

With the advent of a variety of vaccines against viral infections, there are multiple viruses that can be prevented via vaccination. However, breakthrough infections or uncovered strains can still cause vaccine-preventable viral infections (VPVIs). Therefore, timely diagnosis, treatment, and surveillance of these viruses is critical to patient care and public health. Point-of-care (POC) viral diagnostics tools have brought significant improvements in the detection and management of VPVIs. These cutting-edge technologies enable prompt and accurate results, enhancing patient care by facilitating timely treatment decisions. This review delves into the advancements in POC testing, including antigen/antibody detection and molecular assays, while focusing on their impact on the diagnosis, treatment, and surveillance of VPVIs such as mpox, viral hepatitis, influenza, flaviviruses (dengue, Zika, and yellow fever virus), and COVID-19. The role of POC tests in monitoring viral infection is crucial for tracking disease progression and managing outbreaks. Furthermore, the application of POC diagnostics has shown to be vital for public health strategies. In this review, we also highlight emerging POC technologies such as CRISPR-based diagnostics and smartphone-integrated POC devices, which have proven particularly beneficial in resource-limited settings. We underscore the importance of continued research to optimize these diagnostic tools for wider global use for mpox, viral hepatitis, influenza, dengue, and COVID-19, while also addressing current challenges related to their sensitivity, specificity, availability, efficiency, and more. Full article

Objective: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. Methods: The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. Results: YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro. Although YFV 17D did not exhibit a lytic effect against Pan02 mouse cells in vitro, a single intratumoral administration of 17D caused a delay in tumor growth and an increase in median survival by 30%. Multiple injections of 17D did not further improve the effect on tumor growth; however, it notably extended the median survival. Furthermore, preliminary immunization with 17D enhanced its oncotherapeutic effect. Conclusions: Intratumoral administration of yellow fever virus vaccine strain 17D delayed tumor in a murine model of pancreatic cancer. The fact that YFV 17D in vitro affected human cancer cells much more strongly than mouse cancer cells appears promising. Hence, we anticipate that the in vivo efficacy of YFV-17D-based oncolytic therapy will also be higher against human pancreatic carcinomas compared to its effect on the mouse pancreatic tumor. Full article

Background/Objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to estimate the incidence of post-vaccination anaphylaxis across various vaccines in adults. Methods: A comprehensive literature search of PubMed, Embase, Scopus, and Web of Science identified studies on anaphylaxis following vaccination in adults (≥18 years), excluding COVID-19 vaccines. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD42024566928). Random-effects and fixed-effects models were used to pool data and estimate the logit proportion, with the logit-transformed proportion serving as the effect size, thereby allowing for the calculation of event rates. Results: A total of 37 studies were included in the systematic review, with 22 studies contributing to the meta-analysis, representing a combined population of 206,855,261 participants. Most studies focused on influenza vaccines (n = 15). Across all studies, 262 anaphylactic cases were reported, with 153 cases related to influenza vaccines, followed by herpes zoster virus vaccines (38 cases) and yellow fever vaccines (29 cases). Td/Tdap vaccine had the lowest rate (0.0001 per 100,000 participants). The overall random-effects model yielded a logit proportion of −10.45 (95% CI: −12.09 to −8.82, p < 0.001), corresponding to an event rate of 2.91 events per 100,000 subjects (95% CI: 0.56 to 14.73). Sensitivity analysis showed a higher incidence for influenza, hepatitis vaccines, and in vulnerable populations. Conclusions: Anaphylaxis following vaccination in adults is rare but varies by vaccine type. Strengthened monitoring and preparedness are essential, especially in non-medical settings, to ensure a rapid response to anaphylaxis and maintain public confidence in vaccination programs. Full article

Dengue fever, caused by the dengue virus (DENV), poses a significant global health challenge, particularly in tropical and subtropical regions. Recent increases in indigenous DENV cases in Europe are concerning, reflecting rising incidence linked to climate change and the spread of Aedes albopictus mosquitoes. These vectors thrive under environmental conditions like temperature and humidity, which are increasingly influenced by climate change. Additionally, global travel accelerates the cross-border spread of mosquito-borne diseases. DENV manifests clinically in a spectrum from asymptomatic cases to severe conditions like dengue hemorrhagic fever and dengue shock syndrome, influenced by viral serotype and host factors. In 2024, Brazil experienced a fourfold increase in dengue cases compared to 2023, accompanied by higher mortality. Conventional control measures, such as vector control, community engagement, and vaccination, proved insufficient as climate change exacerbated mosquito proliferation, challenging containment efforts. In this regard, our review analyzes prevention measures and therapeutic protocols during the outbreak while addressing DENV transmission dynamics, clinical presentations, and epidemiological shifts. It also evaluates diagnostic strategies combining clinical assessment with serological and molecular testing, providing information to improve diagnostic and preventive measures. The global expansion of dengue-endemic regions, including outbreaks in Europe, highlights the urgent need for enhanced surveillance, proactive interventions, and international collaboration to mitigate the growing threat of Dengue and other arboviruses like West Nile, Zika, Chikungunya, Oropouche, and Yellow Fever viruses. Full article

Flaviviruses are arthropod-borne viruses primarily transmitted through the mosquito Aedes aegypti or Culex genus of mosquitos. These viruses are predominantly found in tropical and subtropical regions of the world with their geographical spread predicted to increase as global temperatures continue to rise. These viruses cause a variety of diseases in humans with the most prevalent being caused by dengue, resulting in hemorrhagic fever and associated sequala. Current approaches for therapeutic control of flavivirus infections are limited, and despite recent advances, there are no approved drugs. Vaccines, available for a few circulating flaviviruses, still have limited potential for controlling contemporary and future outbreaks. Mouse models provide us with a valuable tool to test the effectiveness of drugs and vaccines, yet for many flaviviruses, well-established mouse models are lacking. In this review, we highlight the current state of flavivirus vaccines and therapeutics, as well as our current understanding of mouse models for various flaviviruses. Full article

Background/Objectives: Yellow fever virus (YFV) (Flaviviridae, Orthoflavivirus) is the etiologic agent of yellow fever (YF), a vector-borne disease with significant morbidity and mortality across the tropics and neotropics, despite having a highly efficacious and safe vaccine (17D). Vaccination provides lifelong protection from YF disease mediated by humoral immunity. There are several versions of the original 17D vaccine: 17D-204 (marketed in the USA as YF-VAX, in France as Stamaril, and in China as Tiantan-V), 17D-213 (Russian Federation), and 17DD (by FIOCRUZ in Brazil). Vaccines produced in the US, France, Senegal, China, and Russia represent 17D-204-derived strains, whereas the Brazilian 17DD has a unique passage/attenuation history from 17D-204-derived strains. Their functional differences in the neutralization profiles are not known. Methods: The Plaque Reduction Neutralization Test (PRNT) was used to determine the neutralization profiles of sera from 209 patients that were previously vaccinated with the 17DD strain against both 17D-204 and 17DD. Results: Sera exhibited significantly more efficient neutralization of 17DD (mean reciprocal PRNT₅₀ 183, PRNT₈₀ 86, median reciprocal PRNT₅₀ 80, and PRNT₈₀ 40) compared to 17D-204 (mean reciprocal PRNT₅₀ 91, PRNT₈₀ 33, median reciprocal PRNT₅₀ 40, and PRNT₈₀ 10). Conclusions: Our data indicate antigenic differences between 17D and 17DD vaccines. Full article

Yellow fever (YF), caused by the yellow fever virus (YFV), continually spreads and causes epidemics worldwide, posing a great threat to human health. The live-attenuated YF 17D vaccine (YF-17D) has been licensed for preventing YFV infection and administrated via the intramuscular (i.m.) route. In this study, we sought to determine the immunogenicity and protective efficacy of aerosolized YF-17D via the intratracheal (i.t.) route in mice. YF-17D stocks in liquids were successfully aerosolized into particles of 6 μm. Further in vitro phenotype results showed the aerosolization process did not abolish the infectivity of YF-17D. Meanwhile, a single i.t. immunization with aerosolized YF-17D induced robust humoral and cellular immune responses in A129 mice, which is comparable to that received i.p. immunization. Notably, the aerosolized YF-17D also triggered specific secretory IgA (SIgA) production in bronchoalveolar lavage. Additionally, all immunized animals survived a lethal dose of YFV challenge in mice. In conclusion, our results support further development of aerosolized YF-17D in the future. Full article

The live-attenuated yellow fever 17D strain is a potent vaccine and viral vector. Its manufacture is based on embryonated chicken eggs or adherent Vero cells. Both processes are unsuitable for rapid and scalable supply. Here, we introduce a high-throughput workflow to identify suspension cells that are fit for the high-yield production of live YF17D-based vaccines in an intensified upstream process. The use of an automated parallel ambr15 microbioreactor system for screening and process optimization has led to the identification of two promising cell lines (AGE1.CR.pIX and HEK_Dyn) and the establishment of optimized production conditions, which have resulted in a >100-fold increase in virus titers compared to the current state of the art using adherent Vero cells. The process can readily be scaled up from the microbioreactor scale (15 mL) to 1 L stirred tank bioreactors. The viruses produced are genetically stable and maintain their favorable safety and immunogenicity profile, as demonstrated by the absence of neurovirulence in suckling BALB/c mice and consistent seroprotection in AG129 mice. In conclusion, the presented workflow allows for the rapid establishment of a robust, scalable, and high-yield process for the production of live-attenuated orthoflavivirus vaccines, which outperforms current standards. The approach described here can serve as a model for the development of scalable processes and the optimization of yields for other virus-based vaccines that face challenges in meeting growing demands. Full article

The West Nile Virus (WNV), a member of the family Flaviviridae, is an emerging mosquito-borne flavivirus causing potentially severe infections in humans and animals involving the central nervous system (CNS). Due to its emerging tendency, WNV now occurs in many areas where other flaviviruses are co-occurring. Cross-reactive antibodies with flavivirus infections or vaccination (e.g., tick-borne encephalitis virus (TBEV), Usutu virus (USUV), yellow fever virus (YFV), dengue virus (DENV), Japanese encephalitis virus (JEV)) therefore remain a major challenge in diagnosing flavivirus infections. Virus neutralization tests are considered as reference tests for the detection of specific flavivirus antibodies, but are elaborate, time-consuming and need biosafety level 3 facilities. A simple and straightforward assay for the differentiation and detection of specific WNV IgG antibodies for the routine laboratory is urgently needed. In this study, we compared two commercially available enzyme-linked immunosorbent assays (anti-IgG WNV ELISA and anti-NS1-IgG WNV), a commercially available indirect immunofluorescence assay, and a newly developed in-house ELISA for the detection of WNV-NS1-IgG antibodies. All four tests were compared to an in-house NT to determine both the sensitivity and specificity of the four test systems. None of the assays could match the specificity of the NT, although the two NS1-IgG based ELISAs were very close to the specificity of the NT at 97.3% and 94.6%. The in-house WNV-NS1-IgG ELISA had the best performance regarding sensitivity and specificity. The specificities of the ELISA assays and the indirect immunofluorescence assays could not meet the necessary specificity and/or sensitivity. Full article

In the Americas, wild yellow fever (WYF) is an infectious disease that is highly lethal for some non-human primate species and non-vaccinated people. Specifically, in the Brazilian Atlantic Forest, Haemagogus leucocelaenus and Haemagogus janthinomys mosquitoes act as the major vectors. Despite transmission risk being related to vector densities, little is known about how landscape structure affects vector abundance and movement. To fill these gaps, we used vector abundance data and a model-selection approach to assess how landscape structure affects vector abundance, aiming to identify connecting elements for virus dispersion in the state of São Paulo, Brazil. Our findings show that Hg. leucocelaenus and Hg. janthinomys abundances, in highly degraded and fragmented landscapes, are mainly affected by increases in forest cover at scales of 2.0 and 2.5 km, respectively. Fragmented landscapes provide ecological corridors for vector dispersion, which, along with high vector abundance, promotes the creation of risk areas for WYF virus spread, especially along the border with Minas Gerais state, the upper edges of the Serra do Mar, in the Serra da Cantareira, and in areas of the metropolitan regions of São Paulo and Campinas. Full article

Massive vaccination positively impacted the SARS-CoV-2 pandemic, being a strategy to increase the titers of neutralizing antibodies (NAbs) in the population. Assessing NAb levels and understanding the kinetics of NAb responses is critical for evaluating immune protection. In this study, we optimized and validated a PRNT₅₀ assay to assess 50% virus neutralization and evaluated its accuracy to measure NAbs to the original strain or variant of SARS-CoV-2. The optimal settings were selected, such as the cell (2 × 10⁵ cells/well) and CMC (1.5%) concentrations and the viral input (~60 PFU/well) for PRNT-SARS-CoV-2 with cut-off point = 1.64 log₅ based on the ROC curve (AUC = 0.999). The validated PRNT-SARS-CoV-2 assay presented high accuracy with an intraassay precision of 100% for testing samples with different NAb levels (low, medium, and high titers). The method displays high selectivity without cross-reactivity with dengue (DENV), measles (MV), zika (ZIKV), and yellow fever (YFV) viruses. In addition, the standardized PRNT-SARS-CoV-2 assay presented robustness when submitted to controlled variations. The validated PRNT assay was employed to test over 1000 specimens from subjects with positive or negative diagnoses for SARS-CoV-2 infection. Patients with severe COVID-19 exhibited higher levels of NAbs than those presenting mild symptoms for both the Wuhan strain and Omicron. In conclusion, this study provides a detailed description of an optimized and validated PRNT₅₀ assay to monitor immune protection and to subsidize surveillance policies applied to epidemiologic studies of COVID-19. Full article