scholarly journals Serological Array-in-Well Multiplex Assay Reveals a High Rate of Respiratory Virus Infections and Reinfections in Young Children

mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Anna Kazakova ◽  
Laura Kakkola ◽  
Henna Päkkilä ◽  
Tamara Teros-Jaakkola ◽  
Tero Soukka ◽  
...  
Keyword(s):  
Influenza A ◽  
High Rate ◽  
Microbial Pathogens ◽  
Antibody Detection ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Serum Samples ◽  
Perfect Agreement ◽  
Antibody Levels

ABSTRACT Serological assays are used to diagnose and characterize host immune responses against microbial pathogens. Microarray technologies facilitate high-throughput immunoassays of antibody detection against multiple pathogens simultaneously. To improve survey of influenza A virus (IAV), influenza B virus (IBV), respiratory syncytial virus (RSV), and adenovirus (AdV) antibody levels, we developed a microarray consisting of IAV H1N1, IAV H1N1pdm09 (vaccine), IAV H3N2, IBV Victoria, IBV Yamagata, RSV, AdV type 5 hexon protein, and control antigens printed on the bottom of a microtiter plate well. Bound IgG antibodies were detected with anti-human IgG-coated photon-upconverting nanoparticles and measured with a photoluminescence imager. The performance of the microarray immunoassay (MAIA) was evaluated with serum samples (n = 576) collected from children (n = 288) at 1 and 2 years of age and tested by standard enzyme immunoassays (EIAs) for antibodies to IAV vaccine and RSV. EIAs and MAIA showed substantial to almost perfect agreement (Cohen’s κ, 0.62 to 0.83). Applying MAIA, we found seroprevalences of 55% for IAV H1N1, 54% for IAV vaccine, 30% for IAV H3N2, 24% for IBV Victoria, 25% for IBV Yamagata, 38% for RSV, and 26% for AdV in 1-year-old children (n = 768). By the age of 2 years, IgG seropositivity rates (n = 714) increased to 74% for IAV H1N1, 71% for IAV vaccine, 49% for IAV H3N2, 47% for IBV Yamagata, 49% for IBV Victoria, 68% for RSV, and 58% for AdV. By analyzing increases in antibody levels not biased by vaccinations, we found a reinfection rate of 40% for RSV and 31% for AdV in children between 1 and 2 years of age. IMPORTANCE The multiplex immunoassay was successfully used to simultaneously detect antibodies against seven different viruses. The developed serological microarray is a new promising tool for diagnostic, epidemiological, and seroprevalence analyses of virus infections.

scholarly journals Co-circulation of the two influenza B lineages during 13 consecutive influenza surveillance seasons in Italy, 2004–2017

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Simona Puzelli ◽  
◽  
Angela Di Martino ◽  
Marzia Facchini ◽  
Concetta Fabiani ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Illness ◽  
Influenza Surveillance ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Ha Gene ◽  
B Virus ◽  
B Lineage ◽  
Trivalent Vaccine

Abstract Background Since 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season. Methods From 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene. Results Co-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for > 20% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains. Conclusions This study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004–2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases.

scholarly journals A comparison of influenza and respiratory syncytial virus infections among infants admitted to hospital with acute respiratory infections

1976 ◽  
Vol 77 (3) ◽  
pp. 383-392 ◽  
Author(s):  
E. O. Caul ◽  
D. K. Waller ◽  
S. K. R. Clarke ◽  
B. D. Corner
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Rural Areas ◽  
Influenza A ◽  
Respiratory Infections ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Syncytial Virus ◽  
One Year

SUMMARYAmong 741 children under 5 years admitted to hospital with respiratory infections during two winters, infection with influenza A virus was diagnosed in 70 (9%), with influenza B virus in 8 (1%), and with respiratory syncytial virus (RSV) in 259 (35 %). Both influenza virus and RSV infections were diagnosed most frequently in children under the age of one year, and diagnosed more frequently in males than females. Influenza illnesses were more severe in boys than girls. Both infections occurred more often, but were not more severe, in children from a conurbation than in those from ‘rural’ areas. Convulsions were the cause of 36% of admissions with influenza A infections, but were rare in RSV infections. Bronchiolitis was the reason for 39% of admissions with RSV infections, but was rare in influenza infections. It is suggested that infants admitted to hospital are a good source of influenza virus strains for monitoring arttigenic variation.

scholarly journals Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Megan E. Ermler ◽  
Ericka Kirkpatrick ◽  
Weina Sun ◽  
Rong Hai ◽  
Fatima Amanat ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Antiviral Drug ◽  
Antigenic Drift ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Lethal Challenge ◽  
Public Health Burden ◽  
B Virus

ABSTRACT Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed.

scholarly journals Burden of influenza B virus infections in Scotland in 2012/13 and epidemiological investigations between 2000 and 2012

2014 ◽  
Vol 19 (37) ◽  
Author(s):  
H Harvala ◽  
D Smith ◽  
K Salvatierra ◽  
R Gunson ◽  
B von Wissmann ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Risk Groups ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Tetravalent Vaccine ◽  
B Virus ◽  
Children And Young Adolescents

We describe the burden of influenza B infections in Scotland during a 13-year study period. Influenza A and B viruses cocirculated throughout the period, with numbers of influenza B cases approaching or exceeding those of influenza A during six influenza seasons. Influenza B viruses of both Victoria and Yamagata lineage were detected in two of six seasons investigated. For the 2012/13 season, influenza B accounted for 44.4% of all influenzas, with the highest incidence in those under the age of five years. Influenza B virus infections led to fewer admissions to an intensive care unit (ICU) and a lower mortality rate than influenza A (37 vs 81 ICU admissions and three vs 29 deaths) during the 2012/13 season. However, a quarter of those admitted to ICU with influenza B had not been immunised and 60% had not received specific influenza antiviral therapy. This highlights the need for consistent influenza vaccination and prompt usage of antiviral treatment for identified risk groups. Combining the newly introduced vaccination programme for children with the use of a tetravalent vaccine may provide the opportunity to improve the control of influenza B in those with the highest influenza B burden, children and young adolescents.

scholarly journals Effects of Absolute Humidity, Relative Humidity, Temperature, and Wind Speed on Influenza Activity in Toronto, Ontario, Canada

2019 ◽  
Vol 85 (6) ◽  
Author(s):  
Adriana Peci ◽  
Anne-Luise Winter ◽  
Ye Li ◽  
Saravanamuttu Gnaneshan ◽  
Juan Liu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Relative Humidity ◽  
Influenza A ◽  
Absolute Humidity ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
B Virus ◽  
Influenza Activity ◽  
Temperate Climates

ABSTRACT The occurrence of influenza in different climates has been shown to be associated with multiple meteorological factors. The incidence of influenza has been reported to increase during rainy seasons in tropical climates and during the dry, cold months of winter in temperate climates. This study was designed to explore the role of absolute humidity (AH), relative humidity (RH), temperature, and wind speed (WS) on influenza activity in the Toronto, ON, Canada, area. Environmental data obtained from four meteorological stations in the Toronto area over the period from 1 January 2010 to 31 December 2015 were linked to patient influenza data obtained for the same locality and period. Data were analyzed using correlation, negative binomial regressions with linear predictors, and splines to capture the nonlinear relationship between exposure and outcomes. Our study found a negative association of both AH and temperature with influenza A and B virus infections. The effect of RH on influenza A and B viruses was controversial. Temperature fluctuation was associated with increased numbers of influenza B virus infections. Influenza virus was less likely to be detected from community patients than from patients tested as part of an institutional outbreak investigation. This could be more indicative of nosocomial transmission rather than climactic factors. The nonlinear nature of the relationship of influenza A virus with temperature and of influenza B virus with AH, RH, and temperature could explain the complexity and variation between influenza A and B virus infections. Predicting influenza activity is important for the timing of implementation of disease prevention and control measures as well as for resource allocation. IMPORTANCE This study examined the relationship between environmental factors and the occurrence of influenza in general. Since the seasonality of influenza A and B viruses is different in most temperate climates, we also examined each influenza virus separately. This study reports a negative association of both absolute humidity and temperature with influenza A and B viruses and tries to understand the controversial effect of RH on influenza A and B viruses. This study reports a nonlinear relation between influenza A and B viruses with temperature and influenza B virus with absolute and relative humidity. The nonlinear nature of these relations could explain the complexity and difference in seasonality between influenza A and B viruses, with the latter predominating later in the season. Separating community-based specimens from those obtained during outbreaks was also a novel approach in this research. These findings provide a further understanding of influenza virus transmission in temperate climates.

scholarly journals Transcriptome Analyses Implicate Endogenous Retroviruses Involved in the Host Antiviral Immune System through the Interferon Pathway

2021 ◽  
Author(s):  
Miao Wang ◽  
Liying Wang ◽  
Haizhou Liu ◽  
Jianjun Chen ◽  
Di Liu
Keyword(s):  
Transcriptional Activation ◽  
Measles Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Published Data ◽  
Virus Infections ◽  
Antiviral Immune Response

AbstractHuman endogenous retroviruses (HERVs) are the remains of ancient retroviruses that invaded our ancestors’ germline cell and were integrated into the genome. The expression of HERVs has always been a cause for concern because of its association with various cancers and diseases. However, few previous studies have focused on specific activation of HERVs by viral infections. Our previous study has shown that dengue virus type 2 (DENV-2) infection induces the transcription of a large number of abnormal HERVs loci; therefore, the purpose of this study was to explore the relationship between exogenous viral infection and HERV activation further. In this study, we retrieved and reanalyzed published data on 21 transcriptomes of human cells infected with various viruses. We found that infection with different viruses could induce transcriptional activation of HERV loci. Through the comparative analysis of all viral datasets, we identified 43 key HERV loci that were up-regulated by DENV-2, influenza A virus, influenza B virus, Zika virus, measles virus, and West Nile virus infections. Furthermore, the neighboring genes of these HERVs were simultaneously up-regulated, and almost all such neighboring genes were interferon-stimulated genes (ISGs), which are enriched in the host’s antiviral immune response pathways. Our data supported the hypothesis that activation of HERVs, probably via an interferon-mediated mechanism, plays an important role in innate immunity against viral infections.

scholarly journals Antibody Landscape Analysis following Influenza Vaccination and Natural Infection in Humans with a High-Throughput Multiplex Influenza Antibody Detection Assay

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhu-Nan Li ◽  
Feng Liu ◽  
F. Liaini Gross ◽  
Lindsay Kim ◽  
Jill Ferdinands ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccination ◽  
High Throughput ◽  
Influenza A ◽  
Antibody Responses ◽  
Landscape Analysis ◽  
Antibody Detection ◽  
Influenza B Virus ◽  
Influenza B ◽  
Detection Assay

ABSTRACT To better understand the antibody landscape changes following influenza virus natural infection and vaccination, we developed a high-throughput multiplex influenza antibody detection assay (MIADA) containing 42 recombinant hemagglutinins (rHAs) (ectodomain and/or globular head domain) from pre-2009 A(H1N1), A(H1N1)pdm09, A(H2N2), A(H3N2), A(H5N1), A(H7N7), A(H7N9), A(H7N2), A(H9N2), A(H13N9), and influenza B viruses. Panels of ferret antisera, 227 paired human sera from vaccinees (children and adults) in 5 influenza seasons (2010 to 2018), and 17 paired human sera collected from real-time reverse transcription-PCR (rRT-PCR)-confirmed influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B virus-infected adults were analyzed by the MIADA. Ferret antisera demonstrated clear strain-specific antibody responses to exposed subtype HA. Adults (19 to 49 years old) had broader antibody landscapes than young children (<3 years old) and older children (9 to 17 years old) both at baseline and post-vaccination. Influenza vaccination and infection induced the strongest antibody responses specific to HA(s) of exposed strain/subtype viruses and closely related strains; they also induced cross-reactive antibodies to an unexposed influenza virus subtype(s), including novel viruses. Subsequent serum adsorption confirmed that the cross-reactive antibodies against novel subtype HAs were mainly induced by exposures to A(H1N1)/A(H3N2) influenza A viruses. In contrast, adults infected by influenza B viruses mounted antibody responses mostly specific to two influenza B virus lineage HAs. Median fluorescence intensities (MFIs) and seroconversion in MIADA had good correlations with the titers and seroconversion measured by hemagglutination inhibition and microneutralization assays. Our study demonstrated that antibody landscape analysis by the MIADA can be used for influenza vaccine evaluations and characterization of influenza virus infections. IMPORTANCE Repeated influenza vaccination and natural infections generate complex immune profiles in humans that require antibody landscape analysis to assess immunity and evaluate vaccines. However, antibody landscape analyses are difficult to perform using traditional assays. Here, we developed a high-throughput, serum-sparing, multiplex influenza antibody detection assay (MIADA) and analyzed the antibody landscapes following influenza vaccination and infection. We showed that adults had broader antibody landscapes than children. Influenza vaccination and infection not only induced the strongest antibody responses to the hemagglutinins of the viruses of exposure, but also induced cross-reactive antibodies to novel influenza viruses that can be removed by serum adsorption. There is a good correlation between the median fluorescence intensity (MFI) measured by MIADA and hemagglutination inhibition/microneutralization titers. Antibody landscape analysis by the MIADA can be used in influenza vaccine evaluations, including the development of universal influenza vaccines and the characterization of influenza virus infections.

scholarly journals A High-throughput Anti-SARS-CoV-2 IgG Testing Platform for COVID-19

2020 ◽  
Author(s):  
Jinwei Du ◽  
Eric Chu ◽  
Dayu Zhang ◽  
Chuanyi M Lu ◽  
Aiguo Zhang ◽  
...  
Keyword(s):  
High Throughput ◽  
Influenza A ◽  
High Sensitivity ◽  
Cross Reactivity ◽  
Antibody Detection ◽  
Influenza B ◽  
Serum Samples ◽  
Igg Antibody ◽  
Percent Agreement ◽  
Previous Infection

Background: Serology tests for detecting the antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can identify previous infection and help to confirm the presence of current infection. Objective: The aim of this study was to evaluate the performances of a newly developed high throughput immunoassay for anti-SARS-CoV-2 IgG antibody detection. Results: Clinical agreement studies were performed in 77 COVID-19 patient serum samples and 226 negative donor serum/plasma samples. Positive percent agreement (PPA) was 42.86% (95% CI: 9.90% to 81.59%), 55.56% (95% CI: 21.20% to 86.30%), and 96.72% (95% CI: 88.65% to 99.60%) for samples collected on 0-7 days, 8-14 days, and ≥15 days from symptom onset, respectively. Negative Percent Agreement (NPA) was 98.23% (95% CI: 95.53% to 99.52%). No cross-reactivity was observed to patient samples positive for IgG antibodies against the following pathogens: HIV, HAV, HBV, RSV, CMV, EBV, Rubella, Influenza A, and Influenza B. Hemoglobin (200 mg/dL), bilirubin (2 mg/dL) and EDTA (10 mM) showed no significant interfering effect on this assay. Conclusion: An anti-SARS-CoV-2 IgG antibody assay with high sensitivity and specificity has been developed. With the high throughput, this assay will speed up the anti-SARS-CoV-2 IgG testing.

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