scholarly journals Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans

2019 ◽  
Author(s):  
Pramila Rijal ◽  
Bei Bei Wang ◽  
Tiong Kit Tan ◽  
Lisa Schimanski ◽  
Philipp Janesch ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza Vaccine ◽  
Influenza Viruses ◽  
List Type ◽  
Human Monoclonal Antibodies ◽  
Human Antibodies ◽  
Trivalent Influenza Vaccine ◽  
H7n9 Infection ◽  
Group 2 ◽  
Group 1

AbstractThe majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time-window as seen in serological studies and the analysis of many murine monoclonal antibodies. We report three broadly reactive human monoclonal antibodies (mAbs) targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from human over a period of a hundred years. The third antibody isolated from a child with acute mild H7N9 infection inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection.ImportanceAntibodies to the influenza NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that for HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive and able to inhibit a wide spectrum of N1 NAs between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy, and that efficacy of influenza vaccines could be enhanced by ensuring appropriate content of NA antigen.Highlights of the paperAntibodies that inhibit influenza viruses with N1 neuraminidase (NA), with broad reactivity for viruses isolated between 1918-2018, can be isolated from human recipients of seasonal influenza vaccineAntibodies targeting N1 NA of human seasonal H1N1 viruses can cross-react with a variety of avian N1 neuraminidasesAcute H7N9 infection can recall memory B cells to N1 NA and elicit cross-reactive antibodies to the group 1 N1 and group 2 N9 NAsAntibodies to N1 NA with this broad reactivity protect against lethal virus challenge

scholarly journals Broadly Inhibiting Antineuraminidase Monoclonal Antibodies Induced by Trivalent Influenza Vaccine and H7N9 Infection in Humans

2019 ◽  
Vol 94 (4) ◽  
Author(s):  
Pramila Rijal ◽  
Bei Bei Wang ◽  
Tiong Kit Tan ◽  
Lisa Schimanski ◽  
Philipp Janesch ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza Vaccine ◽  
Time Window ◽  
Wide Spectrum ◽  
Influenza Viruses ◽  
Human Mabs ◽  
Human Antibodies ◽  
Trivalent Influenza Vaccine ◽  
H5n1 Influenza ◽  
H7n9 Infection

ABSTRACT The majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time window, as seen in serological studies and the analysis of many murine monoclonal antibodies (MAbs). We report three broadly reactive human MAbs targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from humans over a period of a hundred years. The third antibody, isolated from a child with acute mild H7N9 infection, inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection. IMPORTANCE Antibodies to the influenza virus NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that of antibodies to HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive, with the ability to inhibit a wide spectrum of N1 NAs on viruses isolated between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy and that the efficacy of influenza vaccines could be enhanced by ensuring the appropriate content of NA antigen.

scholarly journals Broadly Reactive Human Monoclonal Antibodies Elicited following Pandemic H1N1 Influenza Virus Exposure Protect Mice against Highly Pathogenic H5N1 Challenge

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Raffael Nachbagauer ◽  
David Shore ◽  
Hua Yang ◽  
Scott K. Johnson ◽  
Jon D. Gabbard ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Influenza Viruses ◽  
Health Concern ◽  
Human Monoclonal Antibodies ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Zoonotic Infections ◽  
Stalk Domain ◽  
Group 1

ABSTRACT Broadly cross-reactive antibodies (Abs) that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes, including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (MAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus. The monoclonal antibodies were isolated from individuals shortly following infection with (70-1F02 and 1009-3B05) or vaccination against (05-2G02 and 09-3A01) A(H1N1)pdm09. Three of the MAbs bound HAs from multiple strains of group 1 viruses, and one MAb, 05-2G02, bound to both group 1 and group 2 influenza A virus HAs. All four antibodies prophylactically protected mice against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) strain. Two MAbs, 70-1F02 and 09-3A01, were further tested for their therapeutic efficacy against the same strain and showed good efficacy in this setting as well. One MAb, 70-1F02, cocrystallized with H5 HA and showed heavy-chain-only interactions similar to those seen with the previously described CR6261 anti-stalk antibody. Finally, we show that antibodies that compete with these MAbs are prevalent in serum from an individual recently infected with the A(H1N1)pdm09 virus. The antibodies described here can be developed into broad-spectrum antiviral therapeutics that could be used to combat infections by zoonotic or emerging pandemic influenza viruses. IMPORTANCE The rise in zoonotic infections of humans by emerging influenza viruses is a worldwide public health concern. The majority of recent zoonotic human influenza cases were caused by H7N9 and H5Nx viruses and were associated with high morbidity and mortality. In addition, seasonal influenza viruses are estimated to cause up to 650,000 deaths annually worldwide. Currently available antiviral treatment options include only neuraminidase inhibitors, but some influenza viruses are naturally resistant to these drugs, and others quickly develop resistance-conferring mutations. Alternative therapeutics are urgently needed. Broadly protective antibodies that target the conserved “stalk” domain of the hemagglutinin represent potential potent antiviral prophylactic and therapeutic agents that can assist pandemic preparedness. Here, we describe four human monoclonal antibodies that target conserved regions of influenza HA and characterize their binding spectrum as well as their protective capacity in prophylactic and therapeutic settings against a lethal challenge with a zoonotic influenza virus.

scholarly journals Hemagglutinin Quantitative ELISA-based Potency Assay for Trivalent Seasonal Influenza Vaccine Using Group-Specific Universal Monoclonal Antibodies

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wonil Chae ◽  
Paul Kim ◽  
Hanna Kim ◽  
Yu Cheol Cheong ◽  
Young-Seok Kim ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Influenza Vaccine ◽  
Dynamic Range ◽  
Soluble Form ◽  
Influenza B Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Influenza B ◽  
Potency Assay ◽  
Group 2 ◽  
Group 1

AbstractThe assurance of vaccine potency is important for the timely release and distribution of influenza vaccines. As an alternative to Single Radial Immunodiffusion (SRID), we report a new quantitative enzyme-linked immunosorbent assay (ELISA) for seasonal trivalent influenza vaccine (TIV). The consensus hemagglutinin (cHA) stalks for group 1 influenza A virus (IAV), group 2 IAV, and influenza B virus (IBV) were designed and produced in bacterial recombinant host in a soluble form, and monoclonal antibodies (mAbs) were generated. The group-specific ‘universal’ mAbs (uAbs) bound to various subtypes of HAs in the same group from recombinant hosts, embryonated eggs, and commercial vaccine lots. The calibration curves were generated to assess the sensitivity, specificity, accuracy, and linear dynamic range. The quantitative ELISA was validated for the potency assay of individual components of TIV- H1, H3, and IBV- with good correlation with the SRID method. This new assay could be extended to pandemic or pre-pandemic mock-up vaccines of H5 of group 1 and H7 virus of group 2, and novel HA stalk-based universal vaccines.

Evaluation of Influenza Patients Admitted in 2019–2020 Flu Season

2022 ◽  
Author(s):  
Bahar Öztelcan Gündüz ◽  
Erman Ataş ◽  
Bülent Ünay ◽  
Halit Halil
Keyword(s):  
Physical Examination ◽  
Chronic Diseases ◽  
Influenza A ◽  
Influenza Infection ◽  
Febrile Seizures ◽  
Influenza Viruses ◽  
Influenza B ◽  
Close Monitoring ◽  
Group 2 ◽  
Group 1

Abstract Objective Influenza viruses are among the most common respiratory pathogens for all age groups, and may cause seasonal outbreaks. The aim of our study was to describe the clinical characteristics of influenza cases in the 2019–2020 flu season and to study the risk factors for hospital admission and complications. Methods This was a retrospective study in 251 children (group 1: nonhospitalized; group 2: hospitalized) with influenza in the 2019–2020 flu season. Data on demographic features, influenza type, complaints, complications, and hospitalization length were collected and recorded. Results Influenza A was detected in 199 (79.3%) patients, and influenza B was detected in 52 (20.7%); 43.4% of patients were girls and 56.6% were boys. The mean age of the patients was 3.91 ± 3.3 years (16 days to 18 years). A total of 52 (20.7%) patients were hospitalized. The age of the patients in group 2 was lower than that in group 1 (3.1 vs. 4.2 years, p = 0.03). Group 2 patients were more likely to have creatine kinase (CK) elevation, febrile seizures, and physical examination abnormalities. Group 2 patients were also more likely to have influenza A. Patients with febrile seizures, chronic diseases, abnormal physical examination findings, developed complications, and additional drug use apart from oseltamivir in the treatment were also more likely to require hospitalization. Conclusion Infants and children with chronic diseases, history of febrile seizures, complications, and the use of drugs other than antiviral drugs should be carefully evaluated in case they need hospitalization. Increasing vaccination rates, initiation of antiviral treatment for selected patients, and close monitoring of patients in risk groups can decrease morbidity and mortality. Myalgias are a common complaint in patients with acute influenza infection. Previous studies suggest CK measurement be part of the work-up for the hospitalized patient with acute influenza infection.

scholarly journals Self-Sampling of Oropharyngeal Swabs Among Healthcare Workers for Molecular Detection of Respiratory Viruses: A Valuable Approach for Epidemiological Studies and Surveillance Programs

2020 ◽  
Vol 8 ◽  
Author(s):  
Cristina Galli ◽  
Laura Pellegrinelli ◽  
Gabriele Del Castillo ◽  
Giovanni Forni ◽  
Cecilia Eugenia Gandolfi ◽  
...  
Keyword(s):  
Real Time ◽  
Healthcare Workers ◽  
Molecular Detection ◽  
Respiratory Viruses ◽  
Epidemiological Studies ◽  
Influenza Viruses ◽  
Rt Pcr ◽  
Surveillance Programs ◽  
Group 2 ◽  
Group 1

This study aimed at assessing the validity of self-collected (self-sampled) oropharyngeal (OP) swabs among healthcare workers compared to those collected by trained sentinel general practitioners (GP-sampled) from individuals with influenza-like illness (ILI), to be implemented in epidemiological studies and/or surveillance programs of viral pathogens involved in community respiratory infections. In our study, OP swabs were collected from adults (>18 years) with ILI during the 2018–2019 influenza season. Two groups of samples were considered: group 1−131 self-sampled OP swabs collected by healthcare workers after being trained on the sampling procedure; group 2−131 GP-sampled OP swabs collected from outpatients by sentinel GPs operating within the Italian Influenza Surveillance Network. To assess swabbing quality, following RNA extraction, each sample was tested for the presence of the human ribonuclease P gene (RNP) by in-house real-time reverse transcriptase–polymerase chain reaction (RT-PCR). Samples with a cycle threshold (Ct) <35 were considered adequate for further virological analysis. Influenza viruses (IVs), respiratory syncytial virus (RSV), and rhinovirus (RV) genomes were detected by in-house real-time RT-PCR. All samples were positive to RNP detection with Ct <35. The mean Ct value was similar in the two groups (group 1 vs. group 2: 25.93 ± 2.22 vs. 25.46 ± 2.40; p = 0.10). IVs, RSV, and RV positivity rates were 26.7 vs. 52.7% (p < 0.01), 7.6 vs. 9.9% (p = 0.52), and 21.4 vs. 19.9% (p = 0.76), respectively. Self-sampled OP swabs resulted as valid as GP-sampled OP swabs for molecular detection of respiratory viruses. Self-swabbing can thus be a worthwhile strategy for sample collection to implement molecular surveillance of respiratory pathogens and carry out epidemiological studies, easily reaching a larger population size.

Human and primate monoclonal antibodies for in vivo therapy.

1988 ◽  
Vol 34 (9) ◽  
pp. 1681-1688 ◽  
Author(s):  
P H Ehrlich ◽  
Z A Moustafa ◽  
J C Justice ◽  
K E Harfeldt ◽  
I K Gadi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Western Blot ◽  
Protein A ◽  
Human Chromosomes ◽  
Human Monoclonal Antibodies ◽  
Western Blot Assay ◽  
Human Antibodies ◽  
Low Levels ◽  
High Concentrations

Abstract Human monoclonal antibodies, owing to their decreased immunogenicity, are expected to be an improvement over mouse monoclonal antibodies for in vivo therapy. Human and primate monoclonal antibodies are best produced with a human x mouse heteromyeloma. Several human chromosomes are stable in the human x (human x mouse) hybrids. Chimpanzee anti-digoxin monoclonal antibodies were prepared and characterized. Because they are structurally very similar to human antibodies, they should be well tolerated in humans. The anti-digoxin antibodies can be used for therapy of extreme overdoses or as an in vivo diagnostic tool for slight overdoses. Because the advantage of using human monoclonal antibodies is their lack of immunogenicity, preparation of the antibody must be scrupulous so as not to introduce extraneous immunogens. Analysis to ensure the purity of the preparation can be complicated by the presence of high concentrations of the antibody and the low levels of contamination that must be detected. We describe a Western blot assay for Protein A that is sensitive even in the presence of human IgG.

scholarly journals 2775. Safety and Immunogenicity of a Seasonal Influenza Vaccine and Ad26.RSV.preF Vaccine With and Without Co-Administration: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study in Adults Aged ≥ 60 Years

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S979-S979
Author(s):  
Christy Comeaux ◽  
Arangassery Rosemary Bastian ◽  
Els De Paepe ◽  
Edmund Omoruyi ◽  
Wouter Haazen ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Neutralizing Antibody ◽  
Severe Illness ◽  
Tolerability Profile ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Antibody Titers ◽  
Group 2 ◽  
Tract Infections ◽  
Group 1

Abstract Background Influenza and RSV can cause respiratory tract infections leading to severe illness, hospitalization and mortality in at-risk populations, particularly the elderly. The seasonality of influenza and RSV present the potential to co-administer vaccines. This study aimed to demonstrate the non-inferiority of co-administration of the experimental RSV vaccine Ad26.RSV.preF with an influenza vaccine (Fluarix) vs. Fluarix alone in terms of immunogenicity against influenza. Methods This was a single-center, randomized, double-blind, placebo-controlled Phase 2a study (NCT03339713) in healthy adults ≥60 years old. Volunteers were randomized 1:1 to receive Fluarix + 1 × 1011 vp Ad26.RSV.preF on Day 1 and placebo on Day 29 (Group 1), or Fluarix + placebo on Day 1 and 1 × 1011 vp Ad26.RSV.preF on Day 29 (Group 2). Blood samples were taken prior to each vaccination and at Day 57. The primary endpoints were geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibody titers against Fluarix strains (A/Michigan, A/Hong Kong, B/Brisbane and B/Phuket) and the safety and tolerability of Ad26.RSV.preF administered with or without Fluarix. A key secondary endpoint was neutralizing antibody titers to RSV A2. Results Volunteers (N = 180) were included in Group 1 (n = 90) or Group 2 (n = 90). Most volunteers were white (89%) and female (63%), with a median age of 65 years. Both groups exhibited an increase from baseline in HI antibody response on Day 29. The 95% one-sided upper confidence limit of all GMT ratios were below the non-inferiority margin of 2. The frequency of solicited adverse events (AE) after Ad26.RSV.preF vaccination was similar with and without influenza co-administration. Solicited AEs were mainly of Grade 1 and 2 and of transient duration. Most unsolicited AEs were considered unrelated to the study vaccination and were Grade 1 or 2. There were no serious AEs related to the study vaccine and there were no discontinuations due to AEs. RSV neutralizing antibody titers 29 days post- Ad26.RSV.preF immunization were similar in both groups (1404, Group 1; 1690, Group 2). Conclusion Co-administration of Ad26.RSV.preF with Fluarix was non-inferior to Fluarix alone in terms of immunogenicity against influenza and had an acceptable tolerability profile. Disclosures All authors: No reported disclosures.

scholarly journals Randomized, Controlled Trial of a 13-Valent Pneumococcal Conjugate Vaccine Administered Concomitantly with an Influenza Vaccine in Healthy Adults

2012 ◽  
Vol 19 (8) ◽  
pp. 1296-1303 ◽  
Author(s):  
Robert W. Frenck ◽  
Alejandra Gurtman ◽  
John Rubino ◽  
William Smith ◽  
Martin van Cleeff ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Group 2 ◽  
Group 1

ABSTRACTA randomized, double-blind, phase 3 trial evaluated the immunogenicity, safety, and tolerability of a 13-valent pneumococcal conjugate vaccine (PCV13) coadministered with trivalent inactivated influenza vaccine (TIV) in pneumococcal vaccine-naive adults. Participants ages 50 to 59 years (n= 1,116) received TIV with PCV13 (group 1) or placebo (group 2) (1:1 randomization); 1 month later, group 1 received placebo and group 2 received PCV13. A hemagglutination inhibition (HAI) assay for TIV and a standardized enzyme-linked immunosorbent assay for pneumococcal serotype-specific immunoglobulin G (IgG) were performed and opsonophagocytic activity (OPA) titers (assessedpost hoc) were measured at baseline and 1 and 2 months postvaccination. The rises in HAI assay geometric mean titer (GMT) and percentage of participants in groups 1 and 2 with ≥4-fold increases in HAI responses (A/H1N1, 84.0% and 81.2%, respectively; A/H3N2, 71.1% and 69.5%, respectively; and B, 60.6% and 60.3%, respectively) were similar. In group 1, all serotypes met the predefined IgG geometric mean concentration (GMC) ratio noninferiority criterion relative to group 2, but GMCs were lower in group 1 than group 2. When comparing group 1 with group 2, 5 serotypes did not meet the OPA GMT ratio noninferiority criterion, and OPA GMTs were significantly lower for 10 serotypes. PCV13 injection site reactions were similar and mostly mild in both groups. Systemic events were more frequent in group 1 (86.2%) than group 2 (76.7%;P< 0.001); no vaccine-related serious adverse events occurred. Coadministration of PCV13 and TIV was well tolerated but associated with lower PCV13 antibody responses and is of unknown clinical significance. Given the positive immunologic attributes of PCV13, concomitant administration with TIV should be dictated by clinical circumstances.

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