scholarly journals AS03-adjuvanted H7N9 inactivated split virion vaccines induce cross-reactive and protective responses in ferrets

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Daniel Stadlbauer ◽  
Leon de Waal ◽  
Edith Beaulieu ◽  
Shirin Strohmeier ◽  
Edwin J. B. Veldhuis Kroeze ◽  
...  
Keyword(s):  
Case Fatality ◽  
Influenza Viruses ◽  
Health Concern ◽  
Post Challenge ◽  
The North ◽  
H7n9 Subtype ◽  
Challenge Study ◽  
Eurasian Lineage ◽  
Antibody Titers ◽  
H7 Subtype

AbstractHuman infections with avian H7N9 subtype influenza viruses are a major public health concern and vaccines against H7N9 are urgently needed for pandemic preparedness. In early 2013, novel H7N9 influenza viruses emerged in China that caused about 1600 human cases of infection with a high associated case fatality rate. In this study, two H7N9 split virion vaccines with or without AS03 adjuvant were tested in the naive ferret model. Serological analyses demonstrated that homologous hemagglutination inhibition and microneutralization antibody titers were detectable in the ferrets after the first immunization with the AS03-adjuvanted vaccines that were further boosted by the second immunization. In addition, heterologous antibody titers against older H7 subtype viruses of the North American lineage (H7N7, H7N3) and newer H7 subtype viruses of the Eurasian lineage (H7N9) were detected in the animals receiving the AS03-adjuvanted vaccines. Animals receiving two immunizations of the AS03-adjuvanted vaccines were protected from weight loss and fever in the homologous challenge study and had no detectable virus in throat or lung samples. In addition, microscopic examination post-challenge showed animals immunized with the AS03-adjuvanted vaccines had the least signs of lung injury and inflammation, consistent with the greater relative efficacy of the adjuvanted vaccines. In conclusion, this study demonstrated that the AS03-adjuvanted H7N9 vaccines elicited high levels of homologous and heterologous antibodies and protected against H7N9 virus damage post-challenge.

scholarly journals Performance of BioFire array or QuickVue influenza A + B test versus a validation qPCR assay for detection of influenza A during a volunteer A/California/2009/H1N1 challenge study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
David R. McIlwain ◽  
Han Chen ◽  
Maria Apkarian ◽  
Melton Affrime ◽  
Bonnie Bock ◽  
...  
Keyword(s):  
Influenza A ◽  
Rapid Test ◽  
Influenza Viruses ◽  
Qpcr Assay ◽  
Superior Performance ◽  
Qrt Pcr ◽  
Challenge Study ◽  
Test Kit ◽  
2009 H1n1 ◽  
B Test

Abstract Background Influenza places a significant burden on global health and economics. Individual case management and public health efforts to mitigate the spread of influenza are both strongly impacted by our ability to accurately and efficiently detect influenza viruses in clinical samples. Therefore, it is important to understand the performance characteristics of available assays to detect influenza in a variety of settings. We provide the first report of relative performance between two products marketed to streamline detection of influenza virus in the context of a highly controlled volunteer influenza challenge study. Methods Nasopharyngeal swab samples were collected during a controlled A/California/2009/H1N1 influenza challenge study and analyzed for detection of virus shedding using a validated qRT-PCR (qPCR) assay, a sample-to-answer qRT-PCR device (BioMerieux BioFire FilmArray RP), and an immunoassay based rapid test kit (Quidel QuickVue Influenza A + B Test). Results Relative to qPCR, the sensitivity and specificity of the BioFire assay was 72.1% [63.7–79.5%, 95% confidence interval (CI)] and 93.5% (89.3–96.4%, 95% CI) respectively. For the QuickVue rapid test the sensitivity was 8.5% (4.8–13.7%, 95% CI) and specificity was 99.2% (95.6–100%, 95% CI). Conclusion Relative to qPCR, the BioFire assay had superior performance compared to rapid test in the context of a controlled influenza challenge study.

scholarly journals Modelling local patterns of child mortality risk: a Bayesian Spatio-temporal analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alejandro Lome-Hurtado ◽  
Jacques Lartigue-Mendoza ◽  
Juan C. Trujillo
Keyword(s):  
High Risk ◽  
Mexico City ◽  
Child Mortality ◽  
Mortality Risk ◽  
Temporal Analysis ◽  
Health Concern ◽  
The North ◽  
Greater Mexico ◽  
Spatio Temporal ◽  
Child Mortality Rate

Abstract Background Globally, child mortality rate has remained high over the years, but the figure can be reduced through proper implementation of spatially-targeted public health policies. Due to its alarming rate in comparison to North American standards, child mortality is particularly a health concern in Mexico. Despite this fact, there remains a dearth of studies that address its spatio-temporal identification in the country. The aims of this study are i) to model the evolution of child mortality risk at the municipality level in Greater Mexico City, (ii) to identify municipalities with high, medium, and low risk over time, and (iii) using municipality trends, to ascertain potential high-risk municipalities. Methods In order to control for the space-time patterns of data, the study performs a Bayesian spatio-temporal analysis. This methodology permits the modelling of the geographical variation of child mortality risk across municipalities, within the studied time span. Results The analysis shows that most of the high-risk municipalities were in the east, along with a few in the north and west areas of Greater Mexico City. In some of them, it is possible to distinguish an increasing trend in child mortality risk. The outcomes highlight municipalities currently presenting a medium risk but liable to become high risk, given their trend, after the studied period. Finally, the likelihood of child mortality risk illustrates an overall decreasing tendency throughout the 7-year studied period. Conclusions The identification of high-risk municipalities and risk trends may provide a useful input for policymakers seeking to reduce the incidence of child mortality. The results provide evidence that supports the use of geographical targeting in policy interventions.

scholarly journals Development of an immunochromatographic strip for rapid detection of H7 subtype avian influenza viruses

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ge Li ◽  
Xun Wang ◽  
Qingmei Li ◽  
Jifei Yang ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Point Of Care ◽  
Influenza Viruses ◽  
Control Line ◽  
Avian Influenza Viruses ◽  
Igg Antibody ◽  
Immunochromatographic Strip ◽  
Live Poultry ◽  
Pathogenic Viruses ◽  
H7 Subtype

Abstract Background H7N9 avian influenza virus (AIV) including highly and low pathogenic viruses have been detected in China since 2013. H7N9 AIV has a high mortality rate after infection in humans, and most human cases have close contacted with poultry in the live poultry market. Therefore, it is necessary to develop a rapid point-of-care testing (POCT) technique for H7N9 AIV detection. Methods The H7N9 AIV was inactivated and purified, and was used as the antigen to immunize BALB/c. Twelve H7-HA specific monoclonal antibodies (McAbs) were produced through the hybridoma technique. The McAb 10A8 was conjugated with colloid gold as detecting antibody; McAb 9B6 was dispensed on the nitrocellulose membran as the capture test line and the Goat-anti mouse IgG antibody was dispensed as control line respectively. The immunochromatographic strip was prepared. Results The analysis of ELISA and virus neutralization test showed that the obtained McAbs specifically recognized H7 HA. Based on the prepared strip, the detection of H7 AIV was achieved within 10 min. No cross-reaction occurred between H7 AIVs and other tested viruses. The detection limit of the strip for H7 was 2.4 log10EID50/0.1 mL for chicken swab samples. Conclusion The McAbs were specific for H7 and the immunochromatographic strip developed in this study was convenient, rapid and reliable for the detection of H7 AIV. The strip could provide an effective method for the rapid and early detection of H7 AIV.

scholarly journals PRESENCE OF RESPIRATORY VIRUSES IN EQUINES IN BRAZIL

2014 ◽  
Vol 56 (3) ◽  
pp. 191-195
Author(s):  
Dalva Assunção Portari Mancini ◽  
Aparecida Santo Pietro Pereira ◽  
Rita Maria Zucatelli Mendonça ◽  
Adelia Hiroko Nagamori Kawamoto ◽  
Rosely Cabette Barbosa Alves ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Equine Influenza ◽  
Hemagglutination Inhibition Test ◽  
Parainfluenza Viruses ◽  
Significant Difference ◽  
Antibody Titers ◽  
The Difference

Equines are susceptible to respiratory viruses such as influenza and parainfluenza. Respiratory diseases have adversely impacted economies all over the world. This study was intended to determine the presence of influenza and parainfluenza viruses in unvaccinated horses from some regions of the state of São Paulo, Brazil. Blood serum collected from 72 equines of different towns in this state was tested by hemagglutination inhibition test to detect antibodies for both viruses using the corresponding antigens. About 98.6% (71) and 97.2% (70) of the equines responded with antibody protective titers (≥ 80 HIU/25µL) H7N7 and H3N8 subtypes of influenza A viruses, respectively. All horses (72) also responded with protective titers (≥ 80) HIU/25µL against the parainfluenza virus. The difference between mean antibody titers to H7N7 and H3N8 subtypes of influenza A viruses was not statistically significant (p > 0.05). The mean titers for influenza and parainfluenza viruses, on the other hand, showed a statistically significant difference (p < 0.001). These results indicate a better antibody response from equines to parainfluenza 3 virus than to the equine influenza viruses. No statistically significant differences in the responses against H7N7 and H3N8 subtypes of influenza A and parainfluenza 3 viruses were observed according to the gender (female, male) or the age (≤ 2 to 20 years-old) groups. This study provides evidence of the concomitant presence of two subtypes of the equine influenza A (H7N7 and H3N8) viruses and the parainfluenza 3 virus in equines in Brazil. Thus, it is advisable to vaccinate equines against these respiratory viruses.

scholarly journals Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen

2017 ◽  
Vol 114 (35) ◽  
pp. E7348-E7357 ◽  
Author(s):  
Jesper Pallesen ◽  
Nianshuang Wang ◽  
Kizzmekia S. Corbett ◽  
Daniel Wrapp ◽  
Robert N. Kirchdoerfer ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Case Fatality ◽  
Neutralizing Antibody ◽  
Human Populations ◽  
Receptor Binding Domain ◽  
Potential Mechanism ◽  
Primary Target ◽  
Humoral Immune ◽  
Receptor Recognition ◽  
Antibody Titers

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

scholarly journals Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Bryan S. Kaplan ◽  
Marion Russier ◽  
Trushar Jeevan ◽  
Bindumadhav Marathe ◽  
Elena A. Govorkova ◽  
...  
Keyword(s):  
North America ◽  
Avian Influenza ◽  
North American ◽  
Influenza Viruses ◽  
Morbidity And Mortality ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
The North ◽  
Domestic Poultry ◽  
The Impact

ABSTRACT Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses. Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.

scholarly journals Mutations in the PA Protein of Avian H5N1 Influenza Viruses Affect Polymerase Activity and Mouse Virulence

2017 ◽  
pp. JVI.01557-17 ◽  
Author(s):  
Gongxun Zhong ◽  
Mai Quynh Le ◽  
Tiago J.S. Lopes ◽  
Peter Halfmann ◽  
Masato Hatta ◽  
...  
Keyword(s):  
Amino Acid ◽  
Case Fatality ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Viral Polymerase ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Increased Risk ◽  
Severe Infections ◽  
Viral Determinants

To study the influenza viral determinants of pathogenicity, we characterized two highly pathogenic avian H5N1 influenza viruses isolated in Vietnam in 2012 (A/duck/Vietnam/QT1480/2012; QT1480) and 2013 (A/duck/Vietnam/QT1728/2013; QT1728) and found that the activity of their polymerase complexes differed significantly, even though both viruses were highly pathogenic in mice. Further studies revealed that the PA-S343A/E347D mutations reduced viral polymerase activity and mouse virulence when tested in the genetic background of QT1728 virus. In contrast, the PA-343S/347E mutations increased the polymerase activity of QT1480 and the virulence of a low pathogenic H5N1 influenza virus. The PA-343S residue (which alone increased viral polymerase activity and mouse virulence significantly relative to viral replication complexes encoding PA-343A) is frequently found in H5N1 influenza viruses of several subclades; infection with a virus possessing this amino acid may pose an increased risk to humans.IMPORTANCEH5N1 influenza viruses cause severe infections in humans with a case fatality rate that exceeds 50%. The factors that determine the high virulence of these viruses in humans are not fully understood. Here, we identified two amino acid changes in the viral polymerase PA protein that affect the activity of the viral polymerase complex and virulence in mice. Infection with viruses possessing these amino acid changes may pose an increased risk to humans.

scholarly journals The seasonality of cholera in sub-Saharan Africa

2021 ◽  
Author(s):  
Javier Perez-Saez ◽  
Justin Lessler ◽  
Elizabeth C. Lee ◽  
Francisco J. Luquero ◽  
Espoir B. Malembaka ◽  
...  
Keyword(s):  
Large Scale ◽  
Task Force ◽  
Case Fatality ◽  
Sub Saharan Africa ◽  
Health Concern ◽  
National Differences ◽  
Sub Saharan ◽  
Eastern And Southern Africa ◽  
Positive Correlations ◽  
Gates Foundation

Background Cholera remains a major threat in Sub-Saharan Africa (SSA) where some of the highest case fatality risks are reported. Knowing in what months and where cholera tends to occur across the continent can aid in improving efforts to eliminate cholera as a public health concern; though largely due to lack of unified large-scale datasets, no continent-wide estimates exist. In this study we aim to estimate cholera seasonality across SSA. Methods We leverage the Global Task Force on Cholera Control (GTFCC) global cholera database with statistical models to synthesize data across spatial and temporal scale in order to infer the seasonality of excess suspected cholera occurrence in SSA. We developed a Bayesian statistical model to infer the monthly risk of excess cholera at the first and/or second administrative levels. Seasonality patterns were then grouped into spatial clusters. Finally, we studied the association between seasonality estimates and hydro-climatic variables. Findings The majority of studied countries (24/34) have seasonal patterns in excess cholera, corresponding to approximately 85% of the SSA population. Most countries (19/24) also had sub-national differences in seasonality patterns, with strong differences in seasonality strength between regions. Seasonality patterns clustered into two macro-regions (West Africa and the Sahel vs. Eastern and Southern Africa), which were composed of sub-regional clusters with varying degrees of seasonality. Exploratory association analysis found most consistent and positive correlations between cholera seasonality and precipitation, and to a lesser extent with temperature and flooding. Interpretation Widespread cholera seasonality in SSA offers opportunities for intervention planning. Further studies are needed to study the association between cholera and climate. Funding The NASA Applied Sciences Program and the Bill and Melinda Gates Foundation.

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