Yellow fever is a flavivirus having plus-sensed RNA which encodes a single polyprotein. Host proteases cut this polyprotein into seven nonstructural proteins including a vital NS3 protein. The present study aims to identify the most effective inhibitor against the helicase (NS3) using different advanced ligand and structure-based computational studies. A set of 300 ligands was selected against helicase by chemical structural similarity model, which are similar to S-adenosyl-l-cysteine using infiniSee. This tool screens billions of compounds through a similarity search from in-built chemical spaces (CHEMriya, Galaxi, KnowledgeSpace and REALSpace). The pharmacophore was designed from ligands in the library that showed same features. According to the sequence of ligands, six compounds (29, 87, 99, 116, 148, and 208) were taken for pharmacophore designing against helicase protein. Subsequently, compounds from the library which showed the best pharmacophore shared-features were docked using FlexX functionality of SeeSAR and their optibrium properties were analyzed. Afterward, their ADME was improved by replacing the unfavorable fragments, which resulted in the generation of new compounds. The selected best compounds (301, 302, 303 and 304) were docked using SeeSAR and their pharmacokinetics and toxicological properties were evaluated using SwissADME. The optimal inhibitor for yellow fever helicase was 2-amino-N-(4-(dimethylamino)thiazol-2-yl)-4-methyloxazole-5-carboxamide (302), which exhibits promising potential for drug development.

The plaque reduction neutralization test (PRNT) has been used widely for the detection and quantitation of yellow fever (YF) virus-neutralizing antibodies in human serum; however, it is labor-intensive and challenging to adapt to high-throughput clinical testing needed for vaccine licensure. Here, we describe the development and validation of a new Vero cell-based YF microneutralization (MN) assay, with immunostaining readout, for the detection and quantification of YF virus-neutralizing antibodies in human serum. Comparison of neutralizing antibody titers measured with the YF MN assay versus the historical YF PRNT, based on a 50% reduction in plaque counts (PRNT50), demonstrated 100% serostatus agreement at a titer of 10 (1/dil) in participants with a history of YF vaccination. For validation, intra-assay precision (repeatability), intermediate precision, dilutional accuracy, linearity, specificity, upper limit of quantitation (ULOQ), and lower limit of quantitation (LLOQ) were assessed. The YF MN assay demonstrated suitable intra-assay precision (repeatability) and intermediate precision of 36% and 54%, respectively, with an ULOQ of 10,240. At the lower end of detection, repeatability and intermediate precision were 38% and 41%, respectively, with a LLOQ of 10 (1/dil). Suitable dilutional accuracy, linearity, and specificity across orthoflaviviruses (dengue virus, Japanese encephalitis virus, and Zika virus) and serum matrices (hemolytic, lipemic, and icteric) were also demonstrated. Overall, these promising results led the Center for Biologics Evaluation and Research to confirm the suitability of the validated YF MN assay for the detection and quantification of YF virus-neutralizing antibodies.

With increased globalization and shifting climate patterns, yellow fever (YF) is re-emerging as a global threat. At present, vaccination remains the most effective prevention strategy. This study describes the development and validation of a new YF microneutralization (MN) assay for the detection and quantification of YF virus-neutralizing antibodies in human serum that offers increased throughput compared with the current standard assay. Overall, the YF MN assay demonstrated acceptable intra-assay precision (repeatability), intermediate precision, dilutional accuracy, linearity, and specificity and is suitable for the detection of YF virus-neutralizing antibodies. Further, the Center for Biologics Evaluation and Research (CBER) supports the use of the YF MN assay in the licensure of candidate YF vaccines.

Background: The global burden of mosquito-borne diseases transmitted by Aedes aegypti and Aedes albopictus mosquitoes has become a pressing public health concern. This study sought to quantify and evaluate about eight decades of publication data on the global epidemiological trend of the diseases transmitted by A. aegypti and A. albopictus. Methods: A comprehensive bibliographic review of literature was performed on A. aegypti and A. albopictus transmitted diseases, focusing on disease transmission, epidemiological trends, vector control strategies, surveillance and monitoring, and international collaborations and initiatives. Extensive data were collected from the Web of Science database and analyzed for citation network analysis (CNA) using VoSviewer software. Data were collected from the Web of Science database encompassing various aspects of Aedes-borne diseases. The bibliographic CNA was performed to quantify and analyze the 77 years of data on A. aegypti and A. albopictus transmitted diseases. Results: The analysis included 4149 publications contributed by 13,416 authors from 149 countries. These articles comprised research articles (91.01%), review articles (6.267%), proceeding papers (1.76%), and book chapters (0.92%). The results revealed a cumulative h-index of 134, indicating the impact of the scientific output in this field. Conclusion: This review contributes to the ongoing efforts to mitigate the impact of Aedes-borne diseases and protect public health worldwide. By synthesizing current knowledge and evidence-based practices, the study provides all information related to publications, citations, co-citations, top journal trends, high-impact publications, and collaborations among authors in one place among the data published in the past eight decades on Aedes-borne diseases.

The yellow fever (YF) vaccine is usually produced with egg-based methods, which has limitations, including potential adverse effects and low production yields. Alternatively, producing the vaccine using Vero cells or HEK 293 cells can overcome some of these issues, but these methods are significantly more expensive. In the current study, the YF vaccine candidate 17DD virus was produced in primary chicken embryo fibroblast (CEF) cells. The primary CEF cells isolation from eggs was optimized through a two-step process. In the first step, the important parameters that contribute to the development of the egg embryo, such as egg position, relative humidity (RH), and incubation time are optimized. In second step, primary CEF release parameters namely; trypsin volume and incubation temperature are optimized. Both steps were optimized using statistical methods. Further, the seeding cell density of isolated CEF was also optimized. It was observed that 5 x 104 cells/cm2 gave the highest virus titer of 3.89 million PFU/ml. The 17DD yields achieved in primary CEFs are much higher than egg-based production and it is an economically viable method.

The rise and resurgence of vector-borne diseases (VBDs) in Europe pose an expanding public health challenge, exacerbated by climate change, globalization, and ecological disruptions. Both arthropod-borne viruses (arboviruses) transmitted by ticks such as Crimean-Congo hemorrhagic fever and arboviruses transmitted by mosquitoes like dengue, Chikungunya, Zika, and Japanese encephalitis have broadened their distribution due to rising temperatures, changes in rainfall, and increased human mobility. By emphasizing the importance of interconnected human, animal, and environmental health, integrated One Health strategies are crucial in addressing this complex issue. Europe faces increased risk due to the expanding habitats of disease-carrying organisms, the spread of new species like Aedes albopictus since 2013, and increased movement of infected individuals between countries, leading European countries to implement strategies such as enhanced surveillance systems, public awareness campaigns, and prompt outbreak response strategies. However, the lack of both targeted antiviral therapies and vaccines for many arboviruses, together with undetected or asymptomatic cases, hamper containment efforts. Therefore, it is important to have integrated strategies that combine climate modeling, disease surveillance, and public health interventions to address expected changes in disease patterns due to global changes. This review explores the spread of arboviruses in Europe, highlighting their historical context, current transmission dynamics, and their impact on public health.

Yellow fever (YF) is a major public health concern, particularly in Africa and South America. This study aimed to detect YF in human and mosquito samples to understand transmission dynamics in the Tanzania-Uganda and Tanzania-Kenya cross-border areas.

Blood samples were collected from individuals aged ≥9 months for serological testing. Mosquitoes were captured and tested for YF virus RNA. Logistic regression models were used to predict seroprevalence and associated risk factors.

The overall YF seroprevalence was 12.5%, with higher rates among older individuals (7.0%) and female participants (immunoglobulin [Ig] G 4.4%, IgM 6.0%). Notably, YF virus RNA was detected in three out of 46 pools of 192 mosquitoes. The odds of testing positive for YF IgG were lower among those with primary education compared with college education (AOR = 0.27, CI: 0.08-0.88) and increased with those experiencing muscle pain (AOR = 4.5, CI: 1.08-18.78) while the odds of testing positive to YF IgM increased with being female (AOR = 4.7, CI: 1.5-14.7), traveling to YF endemic areas (AOR = 5.2, CI: 1.35-44.75), exposure to Aedes mosquitoes (AOR = 3.7, CI: 1.27-10.84) and exhibiting bruising (AOR = 13.5, CI: 1.23-145.72) CONCLUSIONS: Although Tanzania has not experienced YF outbreaks, evidence of YF exposure at the studied borders highlights the need for strengthening cross-border surveillance, vector control, and vaccination efforts. Further research is needed to evaluate the country's overall YF risks.

Yellow fever is a vaccine preventable hemorrhagic disease that leads to morbidity and mortality in the affected individuals. The only options for preventing and controlling its spread are through vaccination. Therefore, this study was conducted to estimate yellow fever vaccination coverage and associated factors among under-five children in Kenya. The total weighted samples of 2,844 children aged under-five were included in this study. The data were taken from the Kenyan Demographic and Health Survey 2022. In the multivariable analysis, the adjusted odds ratio with a 95% CI was used to declare significant associations of yellow fever vaccine. The yellow fever vaccine coverage among children aged under-five in Kenya was 18.50%. The significant factors associated with yellow fever vaccine coverage were: the age of the child older than 24 months (AOR = 1.7; 95% CI (1.17-2.58)); higher odds of yellow fever vaccination coverage was observed among older children, place of residence (AOR = 1.76; 95% CI (1.04-2.97)); higher odds was observed among urban residents, maternal education; primary education (AOR = 1.99; 95% CI (1.04-2.97)), secondary education (AOR = 2.85; 95% CI (1.41-5.76)), mothers who attended primary or secondary education have higher odds of yellow fever vaccination coverage, wealth index (AOR = 2.38; 95% CI (1.15-4.91)); higher odds of vaccination coverage was observed among poor households. Yellow fever vaccine coverage among under-five children in Kenya was low and has become an important public health concern. Policymakers and other stakeholders are recommended to focus on vaccination programs to prevent yellow fever disease.

Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants.

In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18-60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1:1:1:1) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination.

All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12-36] vs 28% [five of 18 participants, 10-54]), and erythema (13% [seven of 54 participants, 5-25] vs 39% [seven of 18 participants, 17-64]), with headache (32% [17 of 54 participants, 20-46] vs 44% [eight of 18 participants, 22-69]) and malaise (26% [14 of 54 participants, 15-40] vs 33% [six of 18 participants, 13-59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82-100), 89% (16 participants, 65-99), 100% (18 participants, 82-100), and 94% (17 participants, 73-100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID50 groups, and YF-VAX group, respectively, remained seroprotected through D180.

vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development.

Sanofi.

The revival of the transmission dynamics of mosquito-borne diseases grants striking challenges to public health intensified by climate change worldwide. This inclusive review article examines multidimensional strategies and challenges linked to climate change and the epidemiology of mosquito-borne diseases such as malaria, dengue, Zika, chikungunya, and yellow fever. It delves into how the biology, pathogenic dynamics, and vector distribution of mosquitoes are influenced by continuously rising temperatures, modified rainfall patterns, and extreme climatic conditions. We also highlighted the high likelihood of malaria in Africa, dengue in Southeast Asia, and blowout of Aedes in North America and Europe. Modern predictive tools and developments in surveillance, including molecular gears, Geographic Information Systems (GIS), and remote sensing have boosted our capacity to predict epidemics. Integrated data management techniques and models based on climatic conditions provide a valuable understanding of public health planning. Based on recent data and expert ideas, the objective of this review is to provide a thoughtful understanding of existing landscape and upcoming directions in the control of mosquito-borne diseases regarding changing climate. This review determines emerging challenges and innovative vector control strategies in the changing climatic conditions to ensure public health.

Many vector-borne viruses are re-emerging as public health threats, yet our understanding of the virus-host interactions critical for productive infection remains limited. The ubiquitination of proteins, including host- and pathogen-derived proteins is a highly prominent and consistent post-translational modification that regulates protein function through signaling and degradation. Viral proteins are documented to hijack the host ubiquitination machinery to modulate multiple host processes including antiviral defense mechanisms. The engagement of the host ubiquitination machinery in the post-translational modification of viral proteins to support aspects of the viral life cycle including assembly and egress is also well documented. Exploring the role ubiquitination plays in the life cycle of vector-transmitted viral pathogens will increase the knowledge base pertinent to the impact of host-enabled ubiquitination of viral and host proteins and the consequences on viral pathogenesis. In this review, we explore E3 ligase-regulated ubiquitination pathways functioning as proviral and viral restriction factors in the context of acutely infectious, vector-transmitted viral pathogens and the potential for therapeutically targeting them for countermeasures development.

The live attenuated yellow fever vaccine (YF17D) has caused controversial safety issues in history with low-yield problems, which has led to a large population being unable to be vaccinated and vaccine shortage in facing recent outbreaks. Here, we report a safer live attenuated vaccine candidate, YF17D-Δ77, which contains 77 nucleotides deletion in the 3' untranslated region (3' UTR) of the YF17D genome. YF17D-Δ77 exhibited no neurotropism and decreased viscerotropism and caused significantly lower lethality in mice compared to YF17D. Mechanistically, the deletion enhanced the sensitivity of the virus to type I and type II interferon responses, which hindered viral replication. Encouragingly, YF17D-Δ77 provided comparable immune protection in mice as did YF17D. Even 10 PFU of YF17D-Δ77 completely protected mice against YFV-Asibi challenge. In addition, the Δ77 mutation showed excellent stability after successive passages in Vero cells. Collectively, the data suggest that further development of YF17D-Δ77 as vaccine candidate is warranted.

Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.

Vaccines protect against many infectious diseases, including some that can directly or indirectly cause nervous system damage. Serious neurological consequences of immunization are typically extremely rare, although they have the potential to jeopardize vaccination programmes, as demonstrated most recently during the COVID-19 pandemic. Neurologists have an important role in identifying safety signals at population and individual patient levels, as well as providing advice on the benefit-risk profile of vaccination in cohorts of patients with diverse neurological conditions. This article reviews the links between vaccination and neurological disease and considers how emerging signals can be evaluated and their mechanistic basis identified. We review examples of neurotropic infections with live attenuated vaccines, as well as neuroimmunological and neurovascular sequelae of other types of vaccines. We emphasize that such risks are typically dwarfed by neurological complications associated with natural infection and discuss how the risks can be further mitigated. The COVID-19 pandemic has highlighted the need to rapidly identify and minimize neurological risks of vaccination, and we review the structures that need to be developed to protect public health against these risks in the future.

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.

Yellow Fever (YF) is an acute viral hemorrhagic disease. Uganda is located within the Africa YF belt. Between 2019 and 2022, the Ugandan Health Authorities reported at least one outbreak of YF annually with an estimated 892 suspected cases, on average per year. The persistent recurrence of this disease raises significant concerns about the efficacy of current response strategies and prevention approaches. YF has been recognized as a One Health issue due to its interrelatedness with the animal and environmental domains. Monkeys have been recognized as the virus primary reservoir. The YF virus is transmitted through bites of infected Aedes or Haemagogus species mosquitoes between monkeys and humans. Human activities, monkey health, and environmental health issues (e.g., climate change and land use) impact YF incidence in Uganda. Additionally, disease control programs for other tropical diseases, such as mosquitoes control programs for malaria, impact YF incidence.This review adopts the One Health approach to highlight the limitations in the existing segmented YF control and prevention strategies in Uganda, including the limited health sector surveillance, the geographically localized outbreak response efforts, the lack of a comprehensive vaccination program, the limited collaboration and communication among relevant national and international agencies, and the inadequate vector control practices. Through a One Health approach, we propose establishing a YF elimination taskforce. This taskforce would oversee coordination of YF elimination initiatives, including implementing a comprehensive surveillance system, conducting mass YF vaccination campaigns, integrating mosquito management strategies, and enhancing risk communication. It is anticipated that adopting the One Health approach will reduce the risk of YF incidence and outbreaks.

Yellow Fever (YF) is a viral arbovirosis of Public Health importance. In Brazil, surveillance is focused mainly on detecting epizootic events of Platyrrhini. Herein, we compared the detection and phylogenetic analysis of YF virus in two neotropical primates (NTP), a Callithrix detected in the previous epidemic period (2016-2020), and a Callicebus nigrifons, showing a new introduction of YF in 2023. This paper illustrates the importance of joint actions of laboratory and field teams to ensure quick response to Public Health emergencies, such as the intensification of vaccination of susceptible human populations.

Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2'-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF.

This review utilizes quatitative methods and bibliometric data to analyse the trends of emerging and re-emerging vector-borne diseases, with a focus on their impact on pediatric population. To conduct this analysis, a systematic search of PubMed articles from the past two decades was performed, specifically looking at 26 different vector-borne viruses listed in WHO and CDC list of vector-borne viruses. The review found that diseases like Dengue, Zika, West Nile, and Chikungunya were frequently discussed in the literature. On the other hand, diseases such as Tick-borne encephalitis, Rift Valley fever, Venezuelan equine encephalitis, Sindbis fever, Venezuelan equine encephalitis, Ross River virus, and Eastern equine encephalitis showed an upward trend in publications, indicating potential resurgence. In addition to discussing trends and patterns, the review delves into the clinical manifestations and long-term effects of the top 10 viruses in children. It highlights various factors including deforestation, urbanization, global travel, and immunosuppression that contribute to disease emergence and resurgence. To effectively combat these vector-borne diseases, continuous surveillance is crucial. The review also emphasizes the importance of increased vaccination efforts and targeted research to address the health challenges they pose. IMPACT: This review employs quantitative analysis of publications to elucidate trends in emerging pediatric vector-borne viral diseases over two decades. Dengue, the most prevalent of these diseases, has spread to new regions. New strains of Japanese Encephalitis have caused outbreaks. Resurgence of Tick-borne Encephalitis, West Nile, and Yellow Fever due to vaccine hesitancy has also transpired. Continuous global surveillance, increased vaccination, and research into novel therapeutics are imperative to combat the substantial morbidity and mortality burden these diseases pose for children worldwide.

Arboviruses, i.e., viruses transmitted by blood-sucking arthropods, trigger significant global epidemics. Over the past 20 years, the frequency of the (re-)emergence of these pathogens, particularly those transmitted by Aedes and Culex mosquitoes, has dramatically increased. Therefore, understanding how human behavior is modulating population exposure to these viruses is of particular importance. This synthesis explores human behavioral factors driving human exposure to arboviruses, focusing on household surroundings, socio-economic status, human activities, and demographic factors. Household surroundings, such as the lack of water access, greatly influence the risk of arbovirus exposure by promoting mosquito breeding in stagnant water bodies. Socio-economic status, such as low income or low education, is correlated to an increased incidence of arboviral infections and exposure. Human activities, particularly those practiced outdoors, as well as geographical proximity to livestock rearing or crop cultivation, inadvertently provide favorable breeding environments for mosquito species, escalating the risk of virus exposure. However, the effects of demographic factors like age and gender can vary widely through space and time. While climate and environmental factors crucially impact vector development and viral replication, household surroundings, socio-economic status, human activities, and demographic factors are key drivers of arbovirus exposure. This article highlights that human behavior creates a complex interplay of factors influencing the risk of mosquito-borne virus exposure, operating at different temporal and spatial scales. To increase awareness among human populations, we must improve our understanding of these complex factors.

There are some concerns about the safety of live attenuated yellow fever vaccines (YF-live), particularly viscerotropic adverse events, which have a high mortality rate. The cellular production of the vaccine will not cause these adverse effects and has the potential to extend applicability to those who have allergic reactions, immunosuppression, and age. In this study, inactivated yellow fever (YF) was prepared and adsorbed with Alum/CpG. The cellular and humoral immunities were investigated in a mouse model. The results showed that Alum/CpG (20 μg/mL) could significantly increase the binding and neutralizing activities of the antibodies against YF. Moreover, the antibody level at day 28 after one dose was similar to that of the attenuated vaccine, but significantly higher after two doses. At the same time, Alum/CpG significantly increased the levels of IFN-γ and IL-4 cytokines.

Zika virus (ZIKV) and yellow fever virus (YFV) originated in Africa and expanded to the Americas, where both are co-circulated. It is hypothesized that in areas of high circulation and vaccination coverage against YFV, children of pregnant women have a lower risk of microcephaly. We evaluated the presence and titers of antibodies and outcomes in women who had ZIKV infection during pregnancy. Pregnancy outcomes were classified as severe, moderate, and without any important outcome. An outcome was defined as severe if miscarriage, stillbirth, or microcephaly occurred, and moderate if low birth weight and/or preterm delivery occurred. If none of these events were identified, the pregnancy was defined as having no adverse effects. A sample of 172 pregnant women with an acute ZIKV infection confirmed during pregnancy were collected throughout 2016. About 89% (150 of 169) of them presented immunity against YFV, including 100% (09 of 09) of those who had severe outcomes, 84% (16 of 19) of those who had moderate outcomes, and 89% (125 of 141) of those who had non-outcomes. There was no difference between groups regarding the presence of anti-YFV antibodies (p = 0.65) and YFV titers (p = 0.6). We were unable to demonstrate a protective association between the presence or titers of YFV antibodies and protection against serious adverse outcomes from exposure to ZIKV in utero.

Arboviral diseases comprise a group of important infectious diseases imposing a heavy burden to public health in many locations of the world. Orthoflaviviruses are viruses belonging to the genus Orthoflavivirus; this genus includes some of the most relevant arboviruses to human health. Orthoflaviviruses can infect several different hosts, with some species being transmitted in cycles involving birds and anthropophilic mosquitoes and others transmitted between mammals and mostly Aedes sp. mosquitoes. Some of the most important sylvatic reservoirs of orthoflaviviruses are non-human primates (NHPs). Many flaviviruses that infect NHPs in nature have the potential to cause epidemics in humans, as has been observed in the cases of Orthoflavivirus denguei (dengue virus - DENV), Orthoflavivirus flavi (yellow fever virus - YFV), and Orthoflavivirus zikaense (Zika virus - ZIKV). In this minireview, we discuss important aspects regarding history, ecology involving NHP, distribution, disease outcome, and pathogenesis of these three major orthoflaviviruses that affect humans and NHP and relate this information to the potential of using NHP as experimental models. In addition, we suggest some orthoflaviviruses that could be better investigated, both in nature and in experimental studies, in light of the recent revolution in molecular biology.

Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used.

We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.).

We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures.

Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping.

Zika virus (ZIKV) poses a serious threat to the entire world. The rapid spread of ZIKV and recent outbreaks since 2007 have caused worldwide concern about the virus. Diagnosis is complicated because of the cross-reactivity of the virus with other viral antibodies. Currently, the virus is diagnosed by molecular techniques such as RT-PCR and IgM-linked enzyme immunoassays (MAC-ELISA). Recently, outbreaks and epidemics have been caused by ZIKV, and severe clinical symptoms and congenital malformations have also been associated with the virus. Although most ZIKV infections present with a subclinical or moderate flu-like course of illness, severe symptoms such as Guillain-Barre syndrome in adults and microcephaly in children of infected mothers have also been reported. Because there is no reliable cure for ZIKV and no vaccine is available, the public health response has focused primarily on preventing infection, particularly in pregnant women. A comprehensive approach is urgently needed to combat this infection and stop its spread and imminent threat. In view of this, this review aims to present the current structural and functional viewpoints, structure, etiology, clinical prognosis, and measures to prevent this transmission based on the literature and current knowledge. Moreover, we provide thorough description of the current understanding about ZIKV interaction with receptors, and a comparative examination of its similarities and differences with other viruses.

Species distribution modeling (SDM) has become an increasingly common approach to explore questions about ecology, geography, outbreak risk, and global change as they relate to infectious disease vectors. Here, we conducted a systematic review of the scientific literature, screening 563 abstracts and identifying 204 studies that used SDMs to produce distribution estimates for mosquito species. While the number of studies employing SDM methods has increased markedly over the past decade, the overwhelming majority used a single method (maximum entropy modeling; MaxEnt) and focused on human infectious disease vectors or their close relatives. The majority of regional models were developed for areas in Africa and Asia, while more localized modeling efforts were most common for North America and Europe. Findings from this study highlight gaps in taxonomic, geographic, and methodological foci of current SDM literature for mosquitoes that can guide future efforts to study the geography of mosquito-borne disease risk.

The attenuated yellow fever vaccine (YFV) is offered free of charge to the Brazilian population through the National Immunization Program (NIP). One of the specifications for quality control analyses of the vaccine is the potency determination. This test determines the number of plaque forming units (PFU) in Vero cells. In order to validate the results, the reference material (RM) is analysed in parallel with an established reference vaccine. The aim of this study was to establish certified RM for use as an internal control in the potency assay for the production chain of YFV. The candidate RM homogeneity and stability were determined, and characterized by a collaborative study for further certification. The RM was considered sufficiently homogeneous with average 4.68 log₁₀ IU/HD and stable at (-20 ± 10) ºC and (22.5 ± 2.5) ºC for 715 and 183 days, respectively. When reconstituted and stored in aliquots of 0.6 mL, it was stable at (-20 ± 10) ºC for eight days. But it was not stable at (5 ± 3) ºC for three days. In a collaborative study, two independents' laboratories gave an averaged value of 4.56 ± 0.030 log₁₀ IU/HD. After determining the expanded uncertainty of homogeneity, stability, and characterization, the certified RM lot: 195VFA020Z presented a property value of 4.56 ± 0.22 log₁₀ IU/HD. It was concluded that the new certified RM can be used in routine analysis of a YFV producer, since it has its property value established and it is stable. The possibility of using it in aliquots after reconstitution will also allow the RM to have a much longer shelf life.

The disease burden of yellow fever virus infection (YFV) is quite high in the tropics where vaccination coverage is low. To date, vaccination is the most effective control strategy to mitigate and eliminate the burden of YF disease. The licensed YF vaccines are safe and effective and serious adverse events are rare. Herein, we report three cases of neurological syndrome, compatible with meningoencephalitis following 17DD vaccination. In all cases, YFV-specific IgM antibodies were detected in the cerebrospinal fluid. Our observations confirm the development of YF vaccine-associated neurotropic disease, a rare serious adverse event, from which all three patients have fully recovered without any long-term sequelae. This report reinforces the need for awareness among health professionals to recognize and effectively manage such events in a timely manner.

One of the most effective vaccines against an arbovirus is the YFV-17D live-attenuated vaccine developed in 1937 against Yellow Fever (YF). This vaccine replicates poorly in mosquitoes and consequently, is not transmitted by vectors. Vaccine shortages, mainly due to constrained productions based on pathogen-free embryonated eggs, led Sanofi to move towards alternative methods based on a state-of-the-art process using continuous cell line cultures in bioreactor. vYF-247 is a next-generation live-attenuated vaccine candidate based on 17D adapted to grow in serum-free Vero cells. For the development of a new vaccine, WHO recommends to document infectivity and replication in mosquitoes. Here we infected Aedes aegypti and Aedes albopictus mosquitoes with vYF-247 vaccine compared first to the YF-17D-204 reference Sanofi vaccines (Stamaril and YF-VAX) and a clinical human isolate S-79, provided in a blood meal at a titer of 6.5 Log ffu/mL and secondly, to the clinical isolate only at an increased titer of 7.5 Log ffu/mL. At different days post-infection, virus replication, dissemination and transmission were evaluated by quantifying viral particles in mosquito abdomen, head and thorax or saliva, respectively. Although comparison of vYF-247 to reference vaccines could not be completed to yield significant results, we showed that vYF-247 was not transmitted by both Aedes species, either laboratory strains or field-collected populations, compared to clinical strain S-79 at the highest inoculation dose. Combined with the undetectable to low level viremia detected in vaccinees, transmission of the vYF-247 vaccine by mosquitoes is highly unlikely.

The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through infected mosquitoes and spreads from area to area because of international travel. Being an acute viral hemorrhagic disease, yellow fever can be prevented by an effective, safe, and reliable vaccine, but not be eliminated. Currently, there is no antiviral drug available for its cure. Thus, two series of novel bis(benzofuran−1,3-imidazolidin-4-one)s and bis(benzofuran−1,3-benzimidazole)s were designed and synthesized for the development of anti-YFV lead candidates. Among 23 new bis-conjugated compounds, 4 of them inhibited YFV strain 17D (Stamaril) on Huh-7 cells in the cytopathic effect reduction assays. These conjugates exhibited the most compelling efficacy and selectivity with an EC50 of <3.54 μM and SI of >15.3. The results are valuable for the development of novel antiviral drug leads against emerging diseases.

Mosquitoes (Diptera: Culicidae) are of significant public health importance because of their ability to transmit major diseases to humans and animals, and are considered as the world's most deadly arthropods. In recent decades, climate change and globalization have promoted mosquito-borne diseases' (MBDs) geographic expansion to new areas, such as North African countries, where some of these MBDs were unusual or even unknown. In this review, we summarize the latest data on mosquito vector species distribution and MBDs affecting both human and animals in North Africa, in order to better understand the risks associated with the introduction of new invasive mosquito species such as Aedes albopictus. Currently, 26 mosquito species confirmed as pathogen vectors occur in North Africa, including Aedes (five species), Culex (eight species), Culiseta (one species) and Anopheles (12 species). These 26 species are involved in the circulation of seven MBDs in North Africa, including two parasitic infections (malaria and filariasis) and five viral infections (WNV, RVF, DENV, SINV and USUV). No bacterial diseases have been reported so far in this area. This review may guide research studies to fill the data gaps, as well as helping with developing effective vector surveillance and controlling strategies by concerned institutions in different involved countries, leading to cooperative and coordinate vector control measures.