scholarly journals Influenza A (N1-N9) and Influenza B (B/Vic and B/Yam) Neuraminidase Pseudotypes as Tools for Pandemic Preparedness and Improved Influenza Vaccine design

2021 ◽  
Author(s):  
Kelly A.S. da Costa ◽  
Joanne Marie M. Del Rosario ◽  
Matteo Ferrari ◽  
Sneha Vishwanath ◽  
Benedikt Asbach ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Vaccine Design ◽  
Influenza B ◽  
Pandemic Preparedness ◽  
Post Vaccination ◽  
Vaccine Immunogenicity ◽  
Viral Pseudotypes

AbstractTo better understand how inhibition of the influenza neuraminidase (NA) protein contributes to protection against influenza, and to investigate its breadth and cross-neutralizing activity, we have produced lentiviral vectors pseudotyped with an avian H11 hemagglutinin (HA) and the NA (N1-N9) of all influenza A and (B/Victoria and B/Yamagata) influenza B subtypes. These NA viral pseudotypes (PV) possess stable NA activity and can be utilized as target antigens in in vitro assays to assess vaccine immunogenicity. Employing these NA PV, we have developed an enzyme-linked lectin assay (pELLA) for routine serology to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies, and post-vaccination sera with various influenza antigens. We have also shown that pELLA is more sensitive than the commercially available NA-Fluor™ in detecting NA inhibition in these samples. Our studies may lead to establishing the protective NA titer that contributes to NA-based immunity. This will aid in the design of superior, longer lasting, and more broadly protective vaccines that can be employed together with HA-targeted vaccines in a pre-pandemic approach.

scholarly journals Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results

2016 ◽  
Vol 21 (38) ◽  
Author(s):  
Richard Pebody ◽  
Fiona Warburton ◽  
Joanna Ellis ◽  
Nick Andrews ◽  
Alison Potts ◽  
...  
Keyword(s):  
Primary Care ◽  
United Kingdom ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Immunisation Programme ◽  
Influenza B ◽  
Live Attenuated Influenza Vaccine ◽  
The United Kingdom ◽  
Influenza A H1n1 ◽  
The Uk

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season’s adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0–61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6–64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1–68.6) against influenza B. In 2–17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6–94.3) against influenza B and 41.5% (95% CI: −8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

Characterization and evaluation of monoclonal antibodies developed for typing influenza A and influenza B viruses.

1986 ◽  
Vol 23 (2) ◽  
pp. 240-245 ◽  
Author(s):  
H H Walls ◽  
M W Harmon ◽  
J J Slagle ◽  
C Stocksdale ◽  
A P Kendal
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza A ◽  
Influenza B

Vaccination Schedules

2019 ◽  
Author(s):  
Gee Yen Shin
Keyword(s):  
Hepatitis B ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Online Version ◽  
Influenza B ◽  
Immunisation Schedule ◽  
Influenza A H1n1 ◽  
Green Book ◽  
H3n2 Influenza ◽  
The Uk

The vaccines included in the current UK Immunisation Schedule offer protection against the following pathogens: A. Viruses ● Measles ● Mumps ● Rubella ● Polio ● Human Papilloma Virus (certain serotypes) ● Rotavirus ● Influenza virus (flu A and B) ● Varicella zoster virus (shingles) ● Hepatitis B virus B. Bacteria ● Corynebacterium diphtheriae (Diphtheria) ● Clostridium tetani (Tetanus) ● Bordetella pertussis (Pertussis) ● Haemophilus influenzae type B (Hib) ● Neisseria meningitidis (Meningococcal disease—certain serotypes) ● Streptococcus pneumoniae (Pneumococcal disease—certain serotypes) The UK Immunisation Schedule has evolved over several decades and reflects changes in vaccine development and commercial availability, national and sometimes international disease epidemiology, and the latest expert opinion. It is designed to offer optimal protection against infectious diseases of childhood to infants and children at the most appropriate age. The most up-to-date information about the UK Immunisation Schedule is available on the online version of the Department of Health publication commonly known as the ‘Green Book’: Immunisation Against Infectious Disease Handbook (see Further reading. Various chapters of the online version are updated at regular intervals; thus, it is very important to refer to the online version of the Green Book on the website for current guidance. Changes to the UK Immunisation Schedule are made on the recommendation of the independent Joint Committee on Vaccines and Immunisation (JCVI). Several of the UK Immunisation Schedule vaccines are combined vaccines: ● Measles, mumps, and rubella (MMR). ● Hexavalent diphtheria, tetanus, acellular pertussis, inactivated polio virus, Haemophilus influenza type b, hepatitis B (DTaP/IPV/Hib/HepB). ● Diphtheria, tetanus, acellular pertussis, inactivated polio, and Haemophilus influenzae (DTaP/IPV/Hib). ● Diphtheria, tetanus, acellular pertussis, inactivated polio (DTaP/IPV). ● Tetanus, diphtheria, and inactivated polio (Td/IPV). ● Inactivated influenza vaccine: influenza A H1N1, H3N2, influenza B. ● Live attenuated intranasal influenza vaccine: influenza A H1N1, H3N2, influenza B. In the UK, vaccines against single pathogens covered by the MMR vaccine are not recommended and not available in the National Health Service (NHS). There has been some limited demand for single-target vaccines, e.g. measles, due to misguided and unfounded concerns about the alleged risks of autism following MMR.

scholarly journals Artificial Intelligence Applied to in vitro Gene Expression Testing (IVIGET) to Predict Trivalent Inactivated Influenza Vaccine Immunogenicity in HIV Infected Children

2020 ◽  
Vol 11 ◽  
Author(s):  
Nicola Cotugno ◽  
Veronica Santilli ◽  
Giuseppe Rubens Pascucci ◽  
Emma Concetta Manno ◽  
Lesley De Armas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Artificial Intelligence ◽  
Influenza Vaccine ◽  
Vaccine Immunogenicity

scholarly journals TMPRSS2 Is the Major Activating Protease of Influenza A Virus in Primary Human Airway Cells and Influenza B Virus in Human Type II Pneumocytes

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Hannah Limburg ◽  
Anne Harbig ◽  
Dorothea Bestle ◽  
David A. Stein ◽  
Hong M. Moulton ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infectivity ◽  
Type Ii ◽  
Proteolytic Activation ◽  
Human Airway ◽  
Type Ii Pneumocytes ◽  
Airway Cells

ABSTRACT Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is essential for virus infectivity and spread. We previously demonstrated in vitro that the transmembrane protease TMPRSS2 cleaves influenza A virus (IAV) and influenza B virus (IBV) HA possessing a monobasic cleavage site. Subsequent studies revealed that TMPRSS2 is crucial for the activation and pathogenesis of H1N1pdm and H7N9 IAV in mice. In contrast, activation of H3N2 IAV and IBV was found to be independent of TMPRSS2 expression and supported by an as-yet-undetermined protease(s). Here, we investigated the role of TMPRSS2 in proteolytic activation of IAV and IBV in three human airway cell culture systems: primary human bronchial epithelial cells (HBEC), primary type II alveolar epithelial cells (AECII), and Calu-3 cells. Knockdown of TMPRSS2 expression was performed using a previously described antisense peptide-conjugated phosphorodiamidate morpholino oligomer, T-ex5, that interferes with splicing of TMPRSS2 pre-mRNA, resulting in the expression of enzymatically inactive TMPRSS2. T-ex5 treatment produced efficient knockdown of active TMPRSS2 in all three airway cell culture models and prevented proteolytic activation and multiplication of H7N9 IAV in Calu-3 cells and H1N1pdm, H7N9, and H3N2 IAV in HBEC and AECII. T-ex5 treatment also inhibited the activation and spread of IBV in AECII but did not affect IBV activation in HBEC and Calu-3 cells. This study identifies TMPRSS2 as the major HA-activating protease of IAV in human airway cells and IBV in type II pneumocytes and as a potential target for the development of novel drugs to treat influenza infections. IMPORTANCE Influenza A viruses (IAV) and influenza B viruses (IBV) cause significant morbidity and mortality during seasonal outbreaks. Cleavage of the viral surface glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion and essential for virus infectivity. Inhibition of relevant proteases provides a promising therapeutic approach that may avoid the development of drug resistance. HA of most influenza viruses is cleaved at a monobasic cleavage site, and a number of proteases have been shown to cleave HA in vitro. This study demonstrates that the transmembrane protease TMPRSS2 is the major HA-activating protease of IAV in primary human bronchial cells and of both IAV and IBV in primary human type II pneumocytes. It further reveals that human and murine airway cells can differ in their HA-cleaving protease repertoires. Our data will help drive the development of potent and selective protease inhibitors as novel drugs for influenza treatment.

scholarly journals Immunogenicity and safety of a trivalent inactivated influenza vaccine

2011 ◽  
Vol 51 (1) ◽  
pp. 22 ◽  
Author(s):  
Eddy Fadlyana ◽  
Kusnandi Rusmil ◽  
Novilia Sjafri Bachtiar ◽  
Rachmat Gunadi ◽  
Hadyana Sukandar
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Geometric Mean ◽  
Deltoid Muscle ◽  
Influenza B ◽  
Serious Adverse Events ◽  
Blood Samples ◽  
Adolescents And Adults ◽  
Antibody Titers ◽  
Influenza Prevention

Background Trivalent inactivated influenza vaccines (TIV) containing antigens of two influenza A strains, A(H1N1) and A(H3N2), and one influenza B strain, are the standard {onnulation for influenza prevention. The vaccines must be updated annually to provide optimal protection against the predicted prevalent strains for the next influenza season.Objective To assess the immunogenidty and safety of the inactivated influenza vaccine (Flubio®) in adolescents and adults, 28 days after a single dose.Methods In this experimental, randomized, single-blind, bridging study, we included 60 healthy adolescents and adults. A single, 0.5 mL dose was administered intramuscularly in the deltoid muscle of the left ann. Blood samples were obtained before and 28 days after immunization. Standardized hemagglutination inhibition (HI) test was used to assess antibody response to influenza antigens.Results From January to February 2010, a total of 60 adolescents and adults enrolled in the study, but two participants did not provide the required blood samples. One hundred percent of the subjects had an anti-influenza titer ≥ 1:40 HI units to all three strains, A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Brisbane/60/2008 (P=1.000) after immunization. The Geometric Mean Titers (GMT) after immunization increasedfor all strains: A/Brisbane, 76.4 to 992.7, A/Uruguay, 27.6 to 432.1, and B/Brisbane, 19.9 to 312.7. Twenty eight days after immunization, we found a 4 times increase in antibody titers in 75.8% of the subjects for A/Brisbane, 84.5% for A/Uruguay, and 77.6% for B/Brisbane. We also observed that 100% of seronegative subjects converted to seropositive for all 3 strains. All vaccines were well-tolerated. There were no serious adverse events reported during the study.Conclusion In adolescents and adults, the Flubio® vaccine was immunogenic and safe.

scholarly journals The Panther Fusion System with Open Access Functionality for Laboratory-Developed Tests for Influenza A Virus Subtyping

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Kathleen A. Stellrecht ◽  
Jesse L. Cimino ◽  
Vincente P. Maceira
Keyword(s):  
Open Access ◽  
Influenza A ◽  
Limit Of Detection ◽  
Turnaround Time ◽  
Nucleic Acid Amplification ◽  
Influenza B ◽  
Fusion System ◽  
Valuable Complement ◽  
Syncytial Virus

ABSTRACT Nucleic acid amplification tests, such as PCR, are the method of choice for respiratory virus testing, due to their superior diagnostic accuracy and fast turnaround time. The Panther Fusion (Fusion; Hologic) system has an array of highly sensitive in vitro diagnostic (IVD) real-time PCR assays for respiratory viruses, including an assay for influenza A (FluA) virus, influenza B (FluB) virus, and respiratory syncytial virus (RSV) (FFABR assay). The Fusion system has Open Access functionality to perform laboratory-developed tests (LDTs) alongside IVD assays. We developed two LDTs for FluA virus strain typing on the Panther Fusion instrument, enabling side-by-side testing with the FFABR assay. The LDT-FAST assay uses proprietary primers and probes designed by Hologic for the Prodesse ProFAST+ (PFAST) assay. The exWHO-FAST assay is an expanded redesign of the WHO-recommended reverse transcriptase PCRs (RT-PCRs). To evaluate the performance of these two LDTs, 110 FluA virus-positive samples were tested. Of these, 104 had been subtyped previously; 54 were H3, 46 were 09H1, and 4 were fsH1. All were appropriately subtyped by both LDTs. Of the untyped FluA virus samples, three were subtyped as H3 by both LDTs and two were subtyped as H3 by the LDT-FAST assay only. The sample not subtyped by either LDT was retested with the FFABR assay and was now negative. Limit-of-detection (LOD) analyses were performed with five FluA virus strains. The LDT-FAST LODs were similar to the FFABR assay LODs, while the exWHO-FAST LODs were higher for two H3N2 strains, findings that were explained by analysis of primer/probe homology. In conclusion, either FluA virus typing assay would be a valuable complement to the Panther Fusion respiratory menu given the performance of these LDTs, the system’s full automation, and the ability to split eluates for both IVD and LDT testing.

Influenza Vaccine Effectiveness Among Children for the 2017–2018 Season

2019 ◽  
Vol 9 (4) ◽  
pp. 468-473 ◽  
Author(s):  
Lauren N Powell ◽  
Rodolfo E Bégué
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Season ◽  
Vaccine Effectiveness ◽  
Influenza B ◽  
Immunization Registry ◽  
Previous Season ◽  
Waning Immunity ◽  
Small Benefit ◽  
Susceptible Populations

Abstract Background The 2017–2018 influenza season was of high severity. Circulating influenza strains change periodically, making it important to determine vaccine effectiveness on an annual basis, especially for susceptible populations. The primary aim of our study was to estimate the effectiveness of the influenza vaccine among children. Secondary aims were to assess the effect of previous season vaccination and intraseasonal waning of immunity. Methods Children 6 months to 17 years of age tested for influenza during the 2017–2018 season were included. Clinical charts were reviewed, and immunization status was confirmed via the Louisiana Immunization Registry. Influenza vaccine effectiveness (IVE) was estimated in a test-negative design by comparing vaccination status of influenza-positive vs influenza-negative cases. Results A total of 3595 children were included, 26% of whom tested positive for influenza, mostly type A (79%); 15% had received an influenza vaccine prior to illness: 8% among the influenza-positive and 17% among influenza-negative cases (P <.0001). IVE for the 2017–2018 influenza season was 52% overall (95% confidence interval, 38%–62%), 49% for influenza A, and 60% for influenza B. While receiving current year (2017–2018) vaccine had the most effect, receiving the previous year (2016–2017) vaccine had a small benefit and no interference. We found no evidence of waning immunity of the vaccine for the 2017–2018 season. Conclusions IVE was moderate for children. Previous year vaccination had a small but significant benefit and there was no evidence of waning immunity in our cohort. Ongoing national and local surveillance is important to understand the benefit of influenza vaccination.

scholarly journals Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Urai Chaisri ◽  
Wanpen Chaicumpa
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza A ◽  
Treatment Strategies ◽  
Passive Immunization ◽  
Single Chain ◽  
Effector Functions ◽  
Single Chain Antibodies ◽  
Therapeutic Monoclonal Antibodies

This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be producedin vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients) are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

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