A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins

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.

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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2452 ◽

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.

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Linker and/or transmembrane regions of influenza A/Group-1, A/Group-2, and type B virus hemagglutinins are packed differently within trimers

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/j.bbamem.2011.03.005 ◽

2011 ◽

Vol 1808 (7) ◽

pp. 1843-1854 ◽

Cited By ~ 27

Author(s):

Larisa V. Kordyukova ◽

Marina V. Serebryakova ◽

Anton A. Polyansky ◽

Ekaterina A. Kropotkina ◽

Andrei V. Alexeevski ◽

...

Keyword(s):

Influenza A ◽

Type B ◽

B Virus ◽

Transmembrane Regions ◽

Group 2 ◽

Group 1

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A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1801999115 ◽

2018 ◽

Vol 115 (16) ◽

pp. 4240-4245 ◽

Cited By ~ 12

Author(s):

Rameshwar U. Kadam ◽

Ian A. Wilson

Keyword(s):

Influenza Virus ◽

Small Molecule ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Influenza A ◽

Binding Mode ◽

Host Cells ◽

Viral Pathogen ◽

Group 2 ◽

Group 1

The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N-cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses. X-ray structural characterization of group-1 H5N1 A/Vietnam/1203/2004 (H5/Viet) and group-2 H3N2 A/Hong Kong/1/1968 (H3/HK68) HAs at 2.0-Å and 2.57-Å resolution, respectively, revealed that N-cyclohexyltaurine binds to the heart of the conserved HA RBS. N-cyclohexyltaurine mimics the binding mode of the natural receptor sialic acid and RBS-targeting bnAbs through formation of similar hydrogen bonds and CH-π interactions with the HA. In H3/HK68, N-cyclohexyltaurine also binds to a conserved pocket in the stem region, thereby exhibiting a dual-binding mode in group-2 HAs. These long-awaited structural insights into RBS recognition by a noncarbohydrate-based small molecule enhance our knowledge of how to target this important functional site and can serve as a template to guide the development of novel broad-spectrum small-molecule therapeutics against influenza virus.

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