17DD Yellow Fever Revaccination and Heightened Long-Term Immunity in Populations of Disease-Endemic Areas, Brazil.
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ABSTRACT:
SUBMITTER: Campi-Azevedo AC
PROVIDER: S-EPMC6649311 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Due to the risk of severe vaccine-associated adverse events, yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease. From September 2008 through June 2009, two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deaths (case-fatality, 43%) in the southern state of Rio Grande do Sul and 28 cases with 11 deaths (39%) in Sao Paulo state. Epizootic deaths of non-human primates were reported before and during the outbreak. Over 5.5 million doses of yellow fever vaccine were administered in the two most affected states. Vaccine-associated adverse events were associated with six deaths due to acute viscerotropic disease (0.8 deaths per million doses administered) and 45 cases of acute neurotropic disease (5.6 per million doses administered). Yellow fever vaccine recommendations were revised to include areas in Brazil previously not considered at risk for yellow fever.
| S-EPMC3953027 | biostudies-literature
Project description:Yellow fever virus strain:17DD Raw sequence reads
| PRJNA592122 | ENA
Project description:The present study aims to determine whether 17DD-YF-specific humoral and cellular immunological memory is maintained 8-years after primary vaccination with subdoses (10,447IU;3,013IU;587IU;158IU;31IU). For this purpose, this follow-up study was carried out in a subset of volunteers (n = 98) originally enrolled in the dose-response study in 2009 and 46 non-vaccinated controls. Our results demonstrated that vaccinees, who had seroconverted following primary vaccination and had not been revaccinated, present similar neutralizing antibodies levels and YF-specific cellular memory, particularly CMCD4 and EMCD8 as compared to the reference full dose (27,476IU). Although, PRNT seropositivity rates were similar across subgroups (94, 82, 83, 94, 80, and 91%, correspondingly), only doses above 587IU elicited similar iterative proportion of seropositivity rates, calculated as a progressive decrease on seropositivity rates along time (89, 80, 80, and 91%, respectively) as compared to 158IU and 31IU (68 and 46%, respectively). Noteworthy were the strong positive correlations ("EMCD4,EMCD8" and "TNFCD8,IFNCD8") observed in most subdoses, except for 31IU. Major similarities underscored the preserved antibody titers and the outstanding levels of EMCD8, relevant correlates of protection for YF-specific immunity. These findings provide evidences to support the regular use of dose sparing strategy for YF vaccine in adults.
| S-EPMC6598206 | biostudies-literature
Project description:The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system.
| S-EPMC4570825 | biostudies-literature
Project description:BackgroundThe live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine.MethodsNeutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees.Results and discussionThe results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-? and IL-2) and modulatory cytokines (IL-5 and IL-10).ConclusionsThe analysis of serum biomarkers IFN-? and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.
| S-EPMC4223624 | biostudies-literature
Project description:Yellow fever continues to be an important epidemiological problem in Africa and South America even though the disease can be controlled by vaccination. The vaccine has been produced since 1937 and is based on YFV 17DD chicken embryo infection. However, little is known about the histopathological background of virus infection and replication in this model. Here we show by morphological and molecular methods (brightfield and confocal microscopies, immunofluorescence, nested-PCR and sequencing) the kinetics of YFV 17DD infection in chicken embryos with 9 days of development, encompassing 24 to 96 hours post infection. Our principal findings indicate that the main cells involved in virus production are myoblasts with a mesenchymal shape, which also are the first cells to express virus proteins in Gallus gallus embryos at 48 hours after infection. At 72 hours post infection, we observed an increase of infected cells in embryos. Many sites are thus affected in the infection sequence, especially the skeletal muscle. We were also able to confirm an increase of nervous system infection at 96 hours post infection. Our data contribute to the comprehension of the pathogenesis of YF 17DD virus infection in Gallus gallus embryos.
| S-EPMC4861264 | biostudies-literature
Project description:The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses. Despite their longstanding success, attenuated YF vaccines can cause rare fatal adverse events and are contraindicated for persons with immunosuppression, egg allergy and age < 6 months and >60 years. These drawbacks have encouraged the development of a non-live vaccine. The aim of the present study is to characterize and compare the immunological profile of two adjuvant formulations of an inactivated YF 17DD vaccine candidate. Inactivated YF vaccine formulations based on alum (Al(OH)3) or squalene (AddaVax®) were investigated by immunization of C57BL/6 mice in 3-dose or 2-dose schedules, respectively, and compared with a single dose of attenuated YF virus 17DD. Sera were analyzed by ELISA and Plaque Reduction Neutralization Test (PRNT) for detection of total IgG and neutralizing antibodies against YF virus. In addition, splenocytes were collected to evaluate cellular responses by ELISpot. Both inactivated formulations were able to induce high titers of IgG against YF, although neutralizing antibodies levels were borderline on pre-challenge samples. Analysis of IgG subtypes revealed a predominance of IgG2a associated with improved neutralizing capacity in animals immunized with the attenuated YF vaccine, and a predominance of IgG1 in groups immunized with experimental non-live formulations (alum and AddaVax®). After intracerebral (IC) challenge, attenuated and inactivated vaccine formulations showed an increase in neutralizing antibodies. The AddaVax®-based inactivated vaccine and the attenuated vaccine achieved 100% protection, and alum-based equivalent formulation achieved 70% protection.
| S-EPMC9865672 | biostudies-literature
Project description:BACKGROUND:From the end of 2016 until the beginning of 2019, Brazil faced a massive sylvatic yellow fever (YF) outbreak. The 2016-2019 YF epidemics affected densely populated areas, especially the Southeast region, causing thousands of deaths of humans and non-human primates (NHP). METHODOLOGY/PRINCIPAL FINDINGS:We conducted a molecular investigation of yellow fever virus (YFV) RNA in 781 NHP carcasses collected in the urban, urban-rural interface, and rural areas of Minas Gerais state, from January 2017 to December 2018. Samples were analyzed according to the period of sampling, NHP genera, sampling areas, and sampling areas/NHP genera to compare the proportions of YFV-positive carcasses and the estimated YFV genomic loads. YFV infection was confirmed in 38.1% of NHP carcasses (including specimens of the genera Alouatta, Callicebus, Callithrix, and Sapajus), from the urban, urban-rural interface, and rural areas. YFV RNA detection was positively associated with epidemic periods (especially from December to March) and the rural environment. Higher median viral genomic loads (one million times) were estimated in carcasses collected in rural areas compared to urban ones. CONCLUSIONS/SIGNIFICANCE:The results showed the wide occurrence of YF in Minas Gerais in epidemic and non-epidemic periods. According to the sylvatic pattern of YF, a gradient of viral dissemination from rural towards urban areas was observed. A high YF positivity was observed for NHP carcasses collected in urban areas with a widespread occurrence in 67 municipalities of Minas Gerais, including large urban centers. Although there was no documented case of urban/Aedes YFV transmission to humans in Brazil during the 2016-2019 outbreaks, YFV-infected NHP in urban areas with high infestation by Aedes aegypti poses risks for YFV urban/Aedes transmission and urbanization.
| S-EPMC7535057 | biostudies-literature
Project description:Beginning in late 2016 Brazil faced the worst outbreak of Yellow Fever in recent decades, mainly located in southeastern rural regions of the country. In the present study we characterize the Yellow Fever Virus (YFV) associated with this outbreak in São Paulo State, Brazil. Blood or tissues collected from 430 dead monkeys and 1030 pools containing a total of 5,518 mosquitoes were tested for YFV by quantitative RT-PCR, immunohistochemistry (IHC) and indirect immunofluorescence. A total of 67 monkeys were YFV-positive and 3 pools yielded YFV following culture in a C6/36 cell line. Analysis of five nearly full length genomes of YFV from collected samples was consistent with evidence that the virus associated with the São Paulo outbreak originated in Minas Gerais. The phylogenetic analysis also showed that strains involved in the 2016-2017 outbreak in distinct Brazilian states (i.e., Minas Gerais, Rio de Janeiro, Espirito Santo) intermingled in maximum-likelihood and Bayesian trees. Conversely, the strains detected in São Paulo formed a monophyletic cluster, suggesting that they were local-adapted. The finding of YFV by RT-PCR in five Callithrix monkeys who were all YFV-negative by histopathology or immunohistochemistry suggests that this YFV lineage circulating in Sao Paulo is associated with different outcomes in Callithrix when compared to other monkeys.
| S-EPMC6445104 | biostudies-literature
Project description:African Swine Fever (ASF) is one of the most complex and significant diseases from a sanitary-economic perspective currently affecting the world's swine-farming industry. ASF has been endemic in Sardinia (Italy) since 1978, and several control and eradication programmes have met with limited success. In this traditional ASF endemic area, there are three susceptible host populations for this virus sharing the same habitat: wild boar, farmed domestic pigs and non-registered free-ranging pigs (known as "brado" animals). The main goal of this study was to determine and predict fine-scale spatial interactions of this multi-host system in relation to the epidemiology of ASF in the main endemic area of Sardinia, Montes-Orgosolo. To this end, simultaneous monitoring of GPS-GSM collared wild boar and free-ranging pigs sightings were performed to predict interaction indexes through latent selection difference functions with environmental, human and farming factors. Regarding epidemiological assessment, the spatial inter-specific interaction indexes obtained here were used to correlate ASF notifications in wild boar and domestic pig farms. Daily movement patterns, home ranges (between 120.7 and 2,622.8 ha) and resource selection of wild boar were obtained for the first time on the island. Overall, our prediction model showed the highest spatial interactions between wild boar and free-ranging pigs in areas close to pig farms. A spatially explicit model was obtained to map inter-specific interaction over the complete ASF-endemic area of the island. Our approach to monitoring interaction indexes may help explain the occurrence of ASF notifications in wild boar and domestic pigs on a fine-spatial scale. These results support the recent and effective eradication measures taken in Sardinia. In addition, this methodology could be extrapolated to apply in the current epidemiological scenarios of ASF in Eurasia, where exist multi-host systems involving free-ranging pigs and wild boar.
| S-EPMC7259610 | biostudies-literature