Anti-influenza B virus neuraminidase antibodies and uses thereof
Inventors
Palese, Peter • Krammer, Florian • Wohlbold, Teddy John • Garcia-Sastre, Adolfo
Assignees
Icahn School of Medicine at Mount Sinai
Publication Number
US-12030928-B2
Publication Date
2024-07-09
Expiration Date
2038-04-06
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Abstract
Provided herein are antibodies that bind to neuraminidase (NA) of different strains of influenza B virus, host cells for producing such antibodies, and kits comprising such antibodies. Also provided herein are compositions comprising antibodies that bind to NA of different strains of influenza B virus and methods of using such antibodies to diagnose, prevent or treat influenza virus disease.
Core Innovation
The invention provides antibodies that bind to the neuraminidase (NA) of different strains of influenza B virus, including those of the Victoria and Yamagata lineages. These antibodies inhibit the enzymatic activity of the NA and comprise specific variable heavy and light chain region complementarity determining regions (CDRs). The invention also encompasses compositions comprising such antibodies, host cells and expression vectors for the production of the antibodies, and methods of using the antibodies to diagnose, prevent, or treat influenza virus diseases.
Current influenza B virus infections pose significant health challenges due to antigenic diversity and the limited effectiveness of available antiviral drugs. Influenza B viruses cause substantial morbidity and mortality, including among children, and existing neuraminidase inhibitors like oseltamivir have reduced efficacy against influenza B viruses. There are currently no broadly cross-reactive, protective monoclonal antibodies binding the influenza B virus NA. Thus, there is a need for effective therapies to prevent and treat influenza B virus infections and diseases.
Claims Coverage
The claims address isolated polynucleotides encoding antibodies that bind to influenza B virus neuraminidase and host cells and vectors containing such polynucleotides.
Isolated polynucleotide encoding an antibody with specific CDR amino acid sequences
An isolated polynucleotide sequence encoding an antibody that binds to neuraminidase (NA) of an influenza B virus strain, wherein the antibody comprises specified variable heavy chain region CDRs with amino acid sequences SEQ ID NOs: 67, 68, 69 and variable light chain region CDRs with amino acid sequences SEQ ID NOs: 70, 71, 72.
Isolated polynucleotide encoding an antibody with heavy and light chain variable regions
An isolated polynucleotide sequence encoding an antibody that binds to influenza B virus NA, wherein the heavy chain variable region is at least 95% identical to SEQ ID NO: 65 and the light chain variable region is at least 95% identical to SEQ ID NO: 66.
Expression vectors comprising polynucleotides encoding antibodies
Expression vectors comprising the polynucleotide sequence encoding the antibody with the specific CDRs and variable regions described in the claims, operably linked to regulatory regions.
Isolated host cells comprising the polynucleotides or expression vectors
Isolated host cells comprising the polynucleotide sequences encoding the antibodies or the expression vectors comprising such sequences, including cells engineered to express the antibodies with specified variable heavy and light chain CDR regions or at least 95% identical sequences.
Method of antibody expression
Methods for expressing an antibody by culturing an isolated host cell comprising the polynucleotide or expression vector encoding the antibody and isolating the antibody from the host cell or culture.
The claims focus on isolated polynucleotides encoding antibodies targeting influenza B virus neuraminidase with defined CDR sequences, expression vectors and host cells comprising these polynucleotides, and methods for producing the antibodies in such host cells, covering compositions useful for diagnosis, prevention, and treatment of influenza B virus disease.
Stated Advantages
Broad binding and inhibition across influenza B virus strains of both Victoria and Yamagata lineages spanning over 70 years of antigenic drift.
Antibodies inhibit neuraminidase enzymatic activity and activate immune effector functions such as ADCC.
Demonstrated in vivo efficacy in mouse models with prophylactic and therapeutic protection superior to oseltamivir.
Potential to be developed into novel therapeutics effective against drug-resistant influenza B virus strains.
Documented Applications
Diagnosis of influenza B virus infections using antibodies that bind to influenza B virus neuraminidase.
Prevention of influenza virus disease, particularly influenza B virus disease, by administering antibodies or compositions containing such antibodies to subjects at risk.
Treatment of influenza virus infection or disease, including drug-resistant infections and infections refractory to current antiviral agents, with antibodies that bind to influenza B virus neuraminidase.
Production of antibodies by recombinant expression in host cells comprising polynucleotides encoding antibodies with defined CDRs.
Use of influenza B virus neuraminidase polypeptides and antigenic peptides as immunogens to induce immune responses for prevention of influenza virus disease.
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