Epstein-Barr virus vaccines
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.
1. A nanoparticle comprising a first fusion protein, wherein the first fusion protein comprises a monomeric subunit protein joined to at least one immunogenic portion from a first Epstein-Barr Virus (EBV) envelope protein selected from the group consisting of gp350, gH, gL and gp42,
wherein the monomeric subunit protein is selected from the group consisting of:
a) a monomeric subunit protein comprising at least 25 contiguous amino acids of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26 and SEQ ID NO:29; and,
b) a monomeric subunit protein comprising an amino acid sequence at least about 80% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26 and SEQ ID NO:29;
wherein the first fusion protein self-assembles into a nanoparticle; and, wherein the nanoparticle displays the at least one immunogenic portion on its surface.
2. The nanoparticle of claim 1 , wherein the monomeric subunit protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26 and SEQ ID NO:29.
3. The nanoparticle of claim 1 , wherein the at least one immunogenic portion is selected from the group consisting of:
a) an immunogenic portion comprising at least 100 contiguous amino acids from an amino acid sequence selected from the group consisting of SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:41, SEQ ID NO:44, SEQ ID NO:47, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:62, SEQ ID NO:65 and SEQ ID NO:68; and,
b) an immunogenic portion comprising an amino acid sequence at least 80% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:41, SEQ ID NO:44, SEQ ID NO:47, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:62, SEQ ID NO:65 and SEQ ID NO:68
c) an immunogenic portion comprising at least one domain selected from the group consisting of EBV gp350 Domain I, EBV gp350 Domain II and EBV gp350 Domain III; and,
d) an immunogenic portion comprising the EBV gp350 CR2-binding site.
4. The nanoparticle of claim 1 , wherein the immunogenic portion comprises an amino acid sequence selected from the group consisting of SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:41, SEQ ID NO:44, SEQ ID NO:47, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:62, SEQ ID NO:65 and SEQ ID NO:68.
5. The nanoparticle of claim 1 , wherein the fusion protein comprises an amino acid sequence at least 80% identical to a sequence selected from the group consisting of SEQ ID NO:71, SEQ ID NO:74, SEQ ID NO:77, SEQ ID NO:80, SEQ ID NO:83, SEQ ID NO:86, SEQ ID NO:89, SEQ ID NO:92, SEQ ID NO:95, SEQ ID NO:98, SEQ ID NO:101, SEQ ID NO:104, SEQ ID NO:128, SEQ ID NO:130, SEQ ID NO:134 and SEQ ID NO:146.
6. The nanoparticle of claim 1 , wherein the at least one immunogenic portion comprises at least one domain selected from the group consisting of EBV gp350 Domain I, EBV gp350 Domain II, and EBV gp350 Domain III.
7. The nanoparticle of claim 1 , wherein the at least one immunogenic portion comprises an EBV gp350 complement receptor 2 (CR-2) binding site.
8. The nanoparticle of claim 1 , wherein the monomeric ferritin subunit protein is a hybrid protein comprising at least a portion of a bullfrog ferritin protein joined to at least a portion of a ferritin protein selected from the group consisting of a Helicobacter pylori ferritin protein and an Escherichia coli ferritin protein.
9. A method to elicit an immune response against Epstein-Barr virus in an individual, comprising administering to the individual the nanoparticle of claim 1 .