Epstein-Barr virus vaccines
Inventors
Kanekiyo, Masaru • Nabel, Gary J. • Cohen, Jeffrey • Bu, Wei
Assignees
US Department of Health and Human Services
Publication Number
US-10744199-B2
Publication Date
2020-08-18
Expiration Date
2034-10-10
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Abstract
Vaccines are provided that elicit neutralizing antibodies to Epstein-Barr virus (EBV). Some vaccines comprise nanoparticles that display envelope proteins from EBV on their surface. The nanoparticles comprise fusion proteins comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to at least a portion of an EBV envelope protein. The fusion proteins self-assemble to form the envelope protein-displaying nanoparticles. Such vaccines can be used to vaccinate an individual against infection by different types of Epstein-Barr viruses as well as Epstein-Barr viruses that are antigenically divergent from the virus from which the EBV envelope protein was obtained. Also provided are fusion proteins and nucleic acid molecules encoding such proteins.
Core Innovation
The invention provides novel nanoparticle-based vaccines for Epstein-Barr virus (EBV) that are easily manufactured, potent, and capable of eliciting neutralizing antibodies against EBV. These vaccines comprise nanoparticles displaying envelope proteins from EBV on their surface. The nanoparticles are formed from fusion proteins that include a monomeric subunit of a self-assembly protein, such as ferritin, joined to an immunogenic portion of an EBV envelope protein. The fusion proteins self-assemble to form the envelope protein-displaying nanoparticles, which can vaccinate individuals against different types and antigenically divergent strains of EBV. Also provided are fusion proteins and nucleic acid molecules encoding such proteins.
The problem being addressed is that there currently is no efficacious vaccine for EBV, a virus responsible for infectious mononucleosis and associated with human cancers affecting over 300,000 people annually worldwide. Despite high seroprevalence of EBV infection worldwide, no vaccine exists that effectively prevents infection or robustly protects against EBV. Previous vaccine efforts, including a recombinant gp350 protein vaccine, did not protect against EBV infection though it reduced incidence of mononucleosis. There remains a need for effective EBV vaccines that provide robust protection and elicit neutralizing antibodies.
Claims Coverage
The patent includes one independent claim defining a nanoparticle comprising fusion proteins, with several main inventive features describing the nanoparticle composition and properties.
Nanoparticle comprising fusion protein of SA subunit and EBV envelope protein
The nanoparticle comprises a first fusion protein including a monomeric subunit protein joined to at least one immunogenic portion from a first EBV envelope protein selected from gp350, gH, gL, and gp42. The monomeric subunit protein is selected from monomeric proteins comprising at least 25 contiguous amino acids or at least 80% identical sequences of SEQ ID NOs: 2, 5, 8, 11, 14, 17, 20, 23, 26, and 29. The fusion protein self-assembles into a nanoparticle that displays the immunogenic portion on its surface.
Monomeric subunit protein comprises specific amino acid sequences
The monomeric subunit protein comprises an amino acid sequence selected from SEQ ID NOs: 2, 5, 8, 11, 14, 17, 20, 23, 26, and 29.
Immunogenic portion selection from defined EBV gp350 sequences and domains
The immunogenic portion comprises at least 100 contiguous amino acids or at least 80% identical sequences selected from SEQ ID NOs: 32, 35, 38, 41, 44, 47, 50, 53, 62, 65, and 68; includes at least one domain selected from EBV gp350 Domain I, II, or III; or includes the EBV gp350 CR2-binding site.
Immunogenic portion comprises specific amino acid sequences
The immunogenic portion comprises an amino acid sequence selected from SEQ ID NOs: 32, 35, 38, 41, 44, 47, 50, 53, 62, 65, and 68.
Fusion protein amino acid sequence identity
The fusion protein comprises an amino acid sequence at least 80% identical to sequences from SEQ ID NOs: 71, 74, 77, 80, 83, 86, 89, 92, 95, 98, 101, 104, 128, 130, 134, and 146.
Immunogenic portion includes EBV gp350 domains
The immunogenic portion includes at least one domain selected from EBV gp350 Domain I, Domain II, and Domain III.
Immunogenic portion includes EBV gp350 CR2-binding site
The immunogenic portion includes the EBV gp350 complement receptor 2 (CR2) binding site.
Hybrid monomeric ferritin subunit protein
The monomeric ferritin subunit protein is a hybrid comprising at least a portion of bullfrog ferritin protein joined to at least a portion of a ferritin selected from Helicobacter pylori ferritin protein and Escherichia coli ferritin protein.
The claimed subject matter encompasses nanoparticles formed from fusion proteins of self-assembling monomeric subunits joined to immunogenic portions of EBV envelope proteins, particularly from defined sequences, capable of self-assembly and displaying immunogenic moieties on their surface, thus eliciting neutralizing antibody responses against EBV.
Stated Advantages
The vaccines are easily manufactured, potent, and elicit neutralizing antibodies to Epstein-Barr virus.
Nanoparticles displaying EBV envelope proteins on their surface can elicit protection against different types and antigenically divergent strains of EBV.
The use of self-assembly protein nanotechnology enhances immunogenicity compared to soluble proteins alone.
Fusion proteins allow robust immune responses targeting key viral epitopes such as the gp350 CR2-binding site, a site of vulnerability on EBV.
Documented Applications
Vaccines comprising nanoparticles displaying EBV envelope proteins for vaccination against infection by different types and antigenically divergent Epstein-Barr viruses.
Methods of vaccinating an individual against Epstein-Barr virus by administering nanoparticles comprising fusion proteins that display EBV envelope proteins.
Use of fusion proteins and nucleic acid molecules encoding such fusion proteins for production of EBV vaccines.
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