Broadly reactive immunogens of influenza H3 virus, compositions and methods of use thereof

Inventors

Allen, James Daniel • Ross, Ted Milburn • WONG, Terianne Maiko

Assignees

University of Georgia Research Foundation Inc

Abstract

Provided herein are non-naturally occurring, broadly reactive, pan-epitopic antigens derived from H3 influenza virus that are immunogenic and are capable of eliciting a broadly reactive immune response, such as a broadly reactive neutralizing antibody response, against H3 virus following introduction into a subject. Also provided are non-naturally, broadly reactive occurring immunogens, vaccines, virus-like particles (VLPs) and compositions comprising the immunogens and vaccines. Methods of generating an immune response in a subject by administering the immunogens, vaccines, VLPs, or compositions thereof are provided. In particular, the immunogens comprise the hemagglutinin (HA) protein of H3 influenza virus strains.

Core Innovation

Discloses immunogenic vaccine compositions comprising an isolated, recombinantly-produced, non-naturally occurring, broadly reactive antigen of H3 influenza virus that generates an immune response comprising inhibitory hemagglutinin (HA) antibodies against present and future H3 virus strains. The recombinant H3 virus antigen comprises an amino acid sequence as set forth in any one of SEQ ID NOs: 3, 6, 10, or 11, and is provided with a physiologically acceptable carrier, excipient, or vehicle.

The disclosed subject matter also includes embodiments in which the broadly reactive H3 immunogen is presented as a synthetic protein immunogen and as polynucleotides encoding the immunogen, including recombinant DNA or RNA forms with codon/RNA optimization and vectors. In addition, virus-like particle (VLP) vaccine embodiments are disclosed that comprise HA and optionally other components, formulated with pharmaceutically acceptable carriers and optional adjuvants.

Overarching methods are described for inducing immune responses and for prophylactic and therapeutic treatment and immunization, using the immunogenic compositions to elicit broadly reactive neutralizing/HAI-inhibitory antibodies against present and future H3 strains across antigenic drift and geography, and optionally T-lymphocytes.

Claims Coverage

The claims cover 5 inventive features centered on a broadly reactive H3 influenza vaccine composition defined by specific amino acid sequences and formulated with a physiologically acceptable carrier to generate inhibitory HA antibody responses against present and future H3 virus strains.

The claims primarily cover an immunogenic vaccine composition with a recombinantly-produced, non-naturally occurring, broadly reactive H3 antigen defined by specific SEQ ID NO amino acid sequences, formulated with a physiologically acceptable carrier to generate inhibitory HA antibody responses against present and future H3 strains. Dependent claims further specify neutralizing antibodies, inhibitory antibodies targeting HA/HA1/HA2, and variants using VLP formulation and polynucleotides encoding the recombinant antigen.

Stated Advantages

Documented Applications