scholarly journals Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in VH1-69 Antibody Orientation on the HA Stem

Cell Reports ◽  
2017 ◽  
Vol 20 (12) ◽  
pp. 2935-2943 ◽  
Author(s):  
Shanshan Lang ◽  
Jia Xie ◽  
Xueyong Zhu ◽  
Nicholas C. Wu ◽  
Richard A. Lerner ◽  
...  
Keyword(s):  
Influenza A ◽  
Antibody Orientation ◽  
Group 1

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

Science ◽  
2011 ◽  
Vol 333 (6044) ◽  
pp. 850-856 ◽  
Author(s):  
D. Corti ◽  
J. Voss ◽  
S. J. Gamblin ◽  
G. Codoni ◽  
A. Macagno ◽  
...  
Keyword(s):  
Influenza A ◽  
Plasma Cells ◽  
Neutralizing Antibody ◽  
Group 2 ◽  
Group 1

scholarly journals A Host-Restricted Self-Attenuated Influenza Virus Provides Broad Pan-Influenza A Protection in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjin Kim ◽  
Yucheol Cheong ◽  
Jinhee Lee ◽  
Jongkwan Lim ◽  
Sanguine Byun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Infection Model ◽  
Wild Type ◽  
Group 1

Influenza virus infections can cause a broad range of symptoms, form mild respiratory problems to severe and fatal complications. While influenza virus poses a global health threat, the frequent antigenic change often significantly compromises the protective efficacy of seasonal vaccines, further increasing the vulnerability to viral infection. Therefore, it is in great need to employ strategies for the development of universal influenza vaccines (UIVs) which can elicit broad protection against diverse influenza viruses. Using a mouse infection model, we examined the breadth of protection of the caspase-triggered live attenuated influenza vaccine (ctLAIV), which was self-attenuated by the host caspase-dependent cleavage of internal viral proteins. A single vaccination in mice induced a broad reactive antibody response against four different influenza viruses, H1 and rH5 (HA group 1) and H3 and rH7 subtypes (HA group 2). Notably, despite the lack of detectable neutralizing antibodies, the vaccination provided heterosubtypic protection against the lethal challenge with the viruses. Sterile protection was confirmed by the complete absence of viral titers in the lungs and nasal turbinates after the challenge. Antibody-dependent cellular cytotoxicity (ADCC) activities of non-neutralizing antibodies contributed to cross-protection. The cross-protection remained robust even after in vivo depletion of T cells or NK cells, reflecting the strength and breadth of the antibody-dependent effector function. The robust mucosal secretion of sIgA reflects an additional level of cross-protection. Our data show that the host-restricted designer vaccine serves an option for developing a UIV, providing pan-influenza A protection against both group 1 and 2 influenza viruses. The present results of potency and breadth of protection from wild type and reassortant viruses addressed in the mouse model by single immunization merits further confirmation and validation, preferably in clinically relevant ferret models with wild type challenges.

scholarly journals Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires

Immunity ◽  
2018 ◽  
Vol 48 (1) ◽  
pp. 174-184.e9 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Akiko Watanabe ◽  
Masayuki Kuraoka ◽  
Khoi T. Do ◽  
Charles E. McGee ◽  
...  
Keyword(s):  
B Cells ◽  
Influenza A ◽  
Memory B Cells ◽  
Influenza A Viruses ◽  
Adult Human ◽  
Group 2 ◽  
Group 1

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

2011 ◽  
Vol 1808 (7) ◽  
pp. 1843-1854 ◽  
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

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

2018 ◽  
Vol 115 (16) ◽  
pp. 4240-4245 ◽  
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.

scholarly journals An influenza A hemagglutinin small-molecule fusion inhibitor identified by a new high-throughput fluorescence polarization screen

2020 ◽  
Vol 117 (31) ◽  
pp. 18431-18438 ◽  
Author(s):  
Yao Yao ◽  
Rameshwar U. Kadam ◽  
Chang-Chun David Lee ◽  
Jordan L. Woehl ◽  
Nicholas C. Wu ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
Fluorescence Polarization ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Cyclic Peptide ◽  
Host Cells ◽  
Vitro Assay ◽  
Group 1

Influenza hemagglutinin (HA) glycoprotein is the primary surface antigen targeted by the host immune response and a focus for development of novel vaccines, broadly neutralizing antibodies (bnAbs), and therapeutics. HA enables viral entry into host cells via receptor binding and membrane fusion and is a validated target for drug discovery. However, to date, only a very few bona fide small molecules have been reported against the HA. To identity new antiviral lead candidates against the highly conserved fusion machinery in the HA stem, we synthesized a fluorescence-polarization probe based on a recently described neutralizing cyclic peptide P7 derived from the complementarity-determining region loops of human bnAbs FI6v3 and CR9114 against the HA stem. We then designed a robust binding assay compatible with high-throughput screening to identify molecules with low micromolar to nanomolar affinity to influenza A group 1 HAs. Our simple, low-cost, and efficient in vitro assay was used to screen H1/Puerto Rico/8/1934 (H1/PR8) HA trimer against ∼72,000 compounds. The crystal structure of H1/PR8 HA in complex with our best hit compound F0045(S) confirmed that it binds to pockets in the HA stem similar to bnAbs FI6v3 and CR9114, cyclic peptide P7, and small-molecule inhibitor JNJ4796. F0045 is enantioselective against a panel of group 1 HAs and F0045(S) exhibits in vitro neutralization activity against multiple H1N1 and H5N1 strains. Our assay, compound characterization, and small-molecule candidate should further stimulate the discovery and development of new compounds with unique chemical scaffolds and enhanced influenza antiviral capabilities.

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