Zika virus (ZIKV) emerged as a global public health threat throughout the Americas since 2014. Phylogenetically, the virus is composed of three main lineages, an African, Asian, and American lineage. ...The recent emergence and spread of ZIKV has raised questions regarding the breadth and potency of human primary ZIKV immune sera against antigenically diverse ZIKV. Although ZIKV is thought to compose a single antigenic serotype, in-depth evaluation of the antigenic relatedness of ZIKV across genetic variants has been limited to a relatively small series of early convalescent human immune sera (4-12 weeks) against a limited number (3) of genetic variants. Using virus neutralization assays, we characterize the potency and breadth of twelve primary ZIKV immune sera from adults infected 5 to 38 months previously against a panel of 11 ZIKV isolates from the African, Asian and American lineages. We assess the variability of neutralization potency of immune sera from these subjects and the variability of susceptibility to neutralization for each virus isolate. Overall, we found all sera neutralized all viruses at FRNT50 ranging from 1:271 to 1:4271, a 15.8-fold range, with only small differences between subject geometric mean titers (GMT) against all viruses and small differences between each ZIKV isolate and sensitivity to neutralization by all sera: when pooled, African strains were 1.3-fold more sensitive to neutralization by subject immune sera compared to pooled American strains. Finally, we subjected our data to analysis using antigenic cartography, finding that ZIKV are highly antigenically similar, with only a ~4-fold range across all antigenic distances between viruses, consistent with a single serotype.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The once-in-a-lifetime recommendation for vaccination against yellow fever virus (YFV) has been controversial, leading to increased scrutiny of the durability of immunity after ...17D vaccination.
Methods
This is a cross-sectional analysis of 17D vaccinees living in nonendemic Portland, Oregon. Neutralization assays were used to determine YFV immunity. The relationships between 17D immunity and vaccination history, demographics, and travel were evaluated using nominal logistic regression.
Results
Seventy-one of 92 (77.2%) subjects were YFV seropositive (90 percent plaque reduction neutralization test ≥1:10) at all timepoints, and 24 of 38 (63.8%) were YFV seropositive at ≥10 years after single-dose vaccination. No relationship was found between YFV immunity and time in endemic countries, other flavivirus immunity, or demographics. Subjects were most likely to become seronegative between 3 and 12 years postvaccination (logistic regression, odds ratio OR = 1.75; 95% confidence interval CI, 1.12–2.73). A comparison of our results and 4 previous studies of YFV nonendemic vaccinees found that overall, 79% (95% CI, 70%–86%) of vaccinees are likely to be seropositive ≥10 years postvaccination.
Conclusions
These results suggest that 1 in 5 17D vaccinees will lack neutralizing antibodies at ~10 years postvaccination, and a booster vaccination should be considered for nonendemic vaccinees before travel to regions where there is a high risk of YFV transmission.
Neutralizing antibody responses after single-dose vaccination with the yellow fever vaccine 17D remain high 0–3 years postvaccination but fall below a widely used neutralization threshold in a subset of vaccinees 3–12 years postvaccination.
Under-recognition of dengue infection may lead to increased morbidity and mortality, whereas early detection is shown to help improve patient outcomes. Recent incidence and outbreak reports of dengue ...virus in the United States and other temperate regions where dengue was not typically seen have raised concerns regarding appropriate diagnosis and management by healthcare providers unfamiliar with the disease. This study aimed to describe self-reported clinical symptoms of dengue fever in a non-endemic cohort and to establish a clinically useful predictive algorithm based on presenting features that can assist in the early evaluation of potential dengue infection. Volunteers who experienced febrile illness while traveling in dengue-endemic countries were recruited for this study. History of illness and blood samples were collected at enrollment. Participants were classified as dengue naive or dengue exposed based on neutralizing antibody titers. Statistical analysis was performed to compare characteristics between the two groups. A regression model including joint/muscle/bone pain, rash, dyspnea, and rhinorrhea predicts dengue infection with 78% sensitivity, 63% specificity, 80% positive predictive value, and 61% negative predictive value. A decision tree model including joint/muscle/bone pain, dyspnea, and rash yields 77% sensitivity and 67% specificity. Diagnosis of dengue fever is challenging because of the nonspecific nature of clinical presentation. A sensitive predicting model can be helpful to triage suspected dengue infection in the non-endemic setting, but specificity requires additional testing including laboratory evaluation.
Designing immunogens and improving delivery methods eliciting protective immunity is a paramount goal of HIV vaccine development. A comparative vaccine challenge study was performed in rhesus ...macaques using clade C HIV Envelope (Env) and SIV Gag antigens. One group was vaccinated using co-immunization with DNA Gag and Env expression plasmids cloned from a single timepoint and trimeric Env gp140 glycoprotein from one of these clones (DNA+Protein). The other group was a prime-boost regimen composed of two replicating simian (SAd7) adenovirus-vectored vaccines expressing Gag and one Env clone from the same timepoint as the DNA+Protein group paired with the same Env gp140 trimer (SAd7+Protein). The env genes were isolated from a single pre-peak neutralization timepoint approximately 1 year post infection in CAP257, an individual with a high degree of neutralization breadth. Both DNA+Protein and SAd7+Protein vaccine strategies elicited significant Env-specific T cell responses, lesser Gag-specific responses, and moderate frequencies of Env-specific T
cells. Both vaccine modalities readily elicited systemic and mucosal Env-specific IgG but not IgA. There was a higher frequency and magnitude of ADCC activity in the SAd7+Protein than the DNA+Protein arm. All macaques developed moderate Tier 1 heterologous neutralizing antibodies, while neutralization of Tier 1B or Tier 2 viruses was sporadic and found primarily in macaques in the SAd7+Protein group. Neither vaccine approach provided significant protection from viral acquisition against repeated titered mucosal challenges with a heterologous Tier 2 clade C SHIV. However, lymphoid and gut tissues collected at necropsy showed that animals in both vaccine groups each had significantly lower copies of viral DNA in individual tissues compared to levels in controls. In the SAd7+Protein-vaccinated macaques, total and peak PBMC viral DNA were significantly lower compared with controls. Taken together, this heterologous Tier 2 SHIV challenge study shows that combination vaccination with SAd7+Protein was superior to combination DNA+Protein in reducing viral seeding in tissues in the absence of protection from infection, thus emphasizing the priming role of replication-competent SAd7 vector. Despite the absence of correlates of protection, because antibody responses were significantly higher in this vaccine group, we hypothesize that vaccine-elicited antibodies contribute to limiting tissue viral seeding.
To investigate whether infection with human immunodeficiency virus 1 (HIV-1) affects fibrosis development in patients infected with Schistosoma mansoni, we evaluated schistosomiasis-induced pathology ...in the livers of Kenyan patients co-infected with HIV-1. Compared with persons with schistosomiasis alone (n = 58), there were no significant differences in distribution of ultrasound-detectable pathology in persons with HIV-1 co-infection (n = 23). Similarly, serum aspartate aminotransferase levels were not significantly different in HIV-1+ individuals. Hepatic fibrosis was associated with significantly decreased CD4+ T cell counts, even in the absence of HIV-1 infection. These data suggest that HIV-1 co-infection does not significantly alter the proportion of patients experiencing schistosomiasis-induced fibrosis, but pathology associated with S. mansoni infections leads to CD4+ T cell reductions and thereby may exacerbate the effects of HIV-1 in co-infected individuals.
The paper begins by outlining the geographical extent of Kenya, its various agroecological zones, and the role of agroforestry in terms of overall development. The paper points out that most ...government departments operate on national levels, and therefore design strategies and approaches to fulfil their policy. The strategies and approaches in extension carried out both by government and non-governmental agencies involved in extension work are discussed For the different areas the paper discuss specific interventions designed to achieve the objectives for undertaking agroforestry activities.The paper concludes that agroforestry interventions need to be broad-based as several approaches are applied in order to meet the pressing needs of rural land users and achieve a developmental goal.
This report describes in detail the process of local level planning in two locations of Nyandarua district, namely Subego, Ndaragua division (June 1993 - March 1995) and Weru, Ol Joro division (April ...1994 - Junne 1995), where this exercise was carried out under the auspices of the first phase of the Nakuru and Nyandarua Intensified Forestry Extension Project.
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