Multivalent nanoparticle-based vaccines
Inventors
Graham, Barney S. • Kanekiyo, Masaru • YASSINE, Hadi M.
Assignees
US Department of Health and Human Services
Publication Number
US-11938221-B2
Publication Date
2024-03-26
Expiration Date
2035-12-31
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Novel, nanoparticle-based vaccines are provided that elicit an immune response to a broad range of infectious agents, such as influenza viruses. The nanoparticles comprise a heterogeneous population of fusion proteins, each comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to one or more immunogenic portions of a protein from an infectious agent, such as influenza virus. The fusion proteins self-assemble to form nanoparticles that display a heterogeneous population of immunogenic portions on their surface. When administered to an individual, such nanoparticles elicit an immune response to different strains, types, subtypes and species with in the same taxonomic family. Thus, such nanoparticles can be used to vaccinate an individual against infection by different Types, subtypes and/or strains of infectious agents. Also provided are specific fusion proteins, nucleic acid molecules encoding such fusion proteins and methods of using nanoparticles of the invention to vaccinate individuals.
Core Innovation
The invention provides novel, nanoparticle-based vaccines that elicit a broadly neutralizing immune response to a range of infectious agents such as influenza virus, HIV and human papilloma virus. These nanoparticles are composed of a heterogeneous population of fusion proteins, each comprising a monomeric subunit of a self-assembling protein, like ferritin, attached to one or more immunogenic portions of a protein from an infectious agent. Upon administration, the nanoparticles display a heterogeneous population of immunogenic portions on their surface, eliciting an immune response to different strains, types, subtypes, and species within the same taxonomic family.
The nanoparticles elicit a broader immune response than vaccines comprising single species of monovalent nanoparticles or mixtures of monovalent nanoparticles. A general embodiment is a nanoparticle made from self-assembling fusion proteins that display immunogenic portions from two or more infectious agents within the same taxonomic family, differing by at least one amino acid in their sequences. In specific embodiments, the immunogenic portions are from corresponding proteins of infectious agents such as various influenza virus strains, subtypes, or types.
The problem solved addresses limitations of current influenza vaccines, which have highly strain-specific efficacy and are produced in embryonated eggs with manufacturing constraints. Existing vaccines induce neutralizing antibodies primarily targeting variable antigenic sites, thus failing to protect against evolving seasonal or pandemic influenza strains. The invention overcomes these issues by providing an easily manufactured, potent vaccine that elicits broadly neutralizing antibodies against heterologous and antigenically divergent influenza viruses as well as other infectious agents.
Claims Coverage
The claims include two independent methods focusing on eliciting a broadly neutralizing immune response and vaccinating against influenza virus using nanoparticles comprising self-assembling fusion proteins.
Nanoparticles comprising at least two species of self-assembling fusion proteins with heterogeneous HA receptor binding domains
The method involves administering to an individual a nanoparticle comprising at least two species of self-assembling fusion proteins, each fusion protein containing a monomeric subunit protein joined to an immunogenic receptor binding domain (RBD) of an influenza virus hemagglutinin (HA) protein. The immunogenic portions differ by at least one amino acid and are displayed on the nanoparticle surface, with at least one species comprising an amino acid sequence at least 80% identical to SEQ ID NO:97.
Nanoparticles comprising at least four species of fusion proteins with differing HA RBD immunogenic portions
The method includes administering a nanoparticle comprising at least four species of self-assembling fusion proteins that differ by at least one amino acid in their immunogenic portion and display these on the nanoparticle surface.
Fusion proteins including specified HA RBD-ferritin sequences
The species of self-assembling fusion proteins comprise amino acid sequences selected from SEQ ID NOs:97, 100, 103, 106, 109, 112, 115, 118, 121, 124, 127, 130, 133, 136, 139, and 142.
The independent claims cover methods of eliciting a broadly neutralizing immune response or vaccinating against influenza virus using nanoparticles displaying heterogeneous fusion proteins with at least two species differing in their hemagglutinin receptor binding domains, incorporating specified amino acid sequences predominantly based on ferritin fusion proteins.
Stated Advantages
Elicits broadly neutralizing antibodies against diverse and heterologous strains of influenza virus.
Easily manufactured nanoparticle-based vaccines.
Greater immune response than monovalent nanoparticles or mixtures of monovalent nanoparticles.
Generates an immune response that can neutralize evolving seasonal and pandemic influenza virus strains.
Documented Applications
Vaccination of individuals to protect against infection by multiple Types, subtypes, strains, or species of influenza virus.
Use in vaccines to elicit broadly neutralizing antibodies against influenza viruses.
Production of novel vaccines against infectious agents including influenza virus, HIV, papillomavirus, flaviviruses, and other viruses listed.
Use of nanoparticles as medicaments or immunogenic compositions for eliciting protective immune responses.
Methods for producing and administering nanoparticle vaccines to elicit immune responses.
Interested in licensing this patent?