Available Technology

Self-Assembled Ferritin Nanoparticles Expressing Hemagglutinin as an Influenza Vaccine

NIH inventors at the Vaccine Research Center have developed a novel influenza virus hemagglutinin (HA)-ferritin nanoparticle influenza vaccine that is easily manufactured, potent, and elicits broadly neutralizing influenza antibodies against multiple strains of influenza. This novel influenza nanoparticle vaccine elicited two types of broadly neutralizing, cross-protective antibodies, one directed to the highly conserved HA stem and a second proximal to the conserved receptor binding site (RBS) of the viral HA, providing a new platform for universal and seasonal influenza. In addition, HA-ferritin nanoparticles can be easily produced from simple expression vectors and without the production of infectious virus in eggs, and will facilitate influenza preparedness in the face of emerging epidemics. This technology exploits ferritin, a ubiquitous iron storage protein, that self-assembles into spherical nanoparticles and could serve as a scaffold to express a heterologous protein, such as influenza HA, so it mimics a physiologically relevant trimeric viral spike. Immunization with the HA-ferritin nanoparticle elicited neutralizing antibody titers that were >10-fold higher than a matched inactivated vaccine. The immune sera raised by HA-ferritin nanoparticles expressing a 1999 HA neutralized seasonal H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This extended neutralization coverage is partially explained by the presence of both type of antibodies, antibodies directed to the conserved HA stem and against the RBS region. Finally, this ferritin nanoparticle vaccine platform has significant advantages in the ability to utilize specific multimerized spikes and it may be applicable to other viral proteins.
Patent Abstract: 
NIH inventors at the Vaccine Research Center have developed a novel influenza virus hemagglutinin (HA)-ferritin nanoparticle influenza vaccine that is easily manufactured, potent, and elicits broadly neutralizing influenza antibodies against multiple strains of influenza. This novel influenza nanoparticle vaccine elicited two types of broadly neutralizing, cross-protective antibodies, one directed to the highly conserved HA stem and a second proximal to the conserved receptor binding site (RBS) of the viral HA, providing a new platform for universal and seasonal influenza. In addition, HA-ferritin nanoparticles can be easily produced from simple expression vectors and without the production of infectious virus in eggs, and will facilitate influenza preparedness in the face of emerging epidemics. This technology exploits ferritin, a ubiquitous iron storage protein, that self-assembles into spherical nanoparticles and could serve as a scaffold to express a heterologous protein, such as influenza HA, so it mimics a physiologically relevant trimeric viral spike. Immunization with the HA-ferritin nanoparticle elicited neutralizing antibody titers that were >10-fold higher than a matched inactivated vaccine. The immune sera raised by HA-ferritin nanoparticles expressing a 1999 HA neutralized seasonal H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This extended neutralization coverage is partially explained by the presence of both type of antibodies, antibodies directed to the conserved HA stem and against the RBS region. Finally, this ferritin nanoparticle vaccine platform has significant advantages in the ability to utilize specific multimerized spikes and it may be applicable to other viral proteins.
Benefits 
Forms an octahedron consisting of 24 subunits, allowing for greatly increased presentation of heterologous protein on the ferritin nanoparticles surface, compared to other vaccine platforms. -In vivodata in multiple animal models demonstrated induction of broader and more potent antibody responses. -Vaccine stimulated broadly neutralizing antibodies against the highly conserved epitope on the HA stem region and against the RBS, thus targeting two independent sites of vulnerability on HA. -Multivalent influenza HA ferritin vaccines have been tested in animal models. -Ferritin is extremely stable to temperature ranges, pH, detergent and other factors. -Easily manufactured, will facilitate influenza preparedness in the face of emerging epidemics.
applications 
Inventors: 
Gary Nabel
Patent Number: 
61/538,663 US Application No. 61/661,209 PCT Appli
Internal Laboratory Ref #: 
E-293-2011/0
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