Ferritin nanoparticle displaying an HIV trimer
The present invention relates to glycosylate HIV timer nanoparticles fused to self-assembling ferritin proteins which may be utilized as immunogens to enhance trafficking to lymph nodes and germinal centers and to heighten immune responses.
1 . A synthetic peptide which comprises a glycosylated Env peptide of HIV and a support peptide, wherein the synthetic peptide forms a self-assembling nanoparticle, wherein the nanoparticle is transported to the follicular dendritic cell (FDC) network and by complement-dependent, mannose-binding-lectin (MBL)-dependent, and/or immunogen-glycan-dependent transport to germinal centers,
wherein the synthetic peptide has the sequence of BG505_MD39_G41_2JD6 (SEQ ID NO:2), BG505_MD39_link14_2JD6 (SEQ ID NO: 3), or BG505_MD39_3bve_m (SEQ ID NO:4),
wherein the Env peptide is glycosylated with oligomannose, and
wherein the support peptide is a ferritin based support peptide.
2 . The synthetic peptide of claim 1 , wherein the support peptide comprises at least 25 contiguous residues having a sequence that is identical to a sequence of at least 25 contiguous amino acids in Pyrococcus furiosus ferritin (SEQ ID NO:5).
3 . A nanoparticle which comprises a plurality of the synthetic peptides of claim 1 .
4 . A nucleic acid encoding the synthetic peptide of claim 1 .
5 . A vector comprising a regulatory element operable in a eukaryotic cell operably linked to the nucleic acid of claim 4 .
6 . The vector of claim 5 , wherein the vector comprises a viral vector.
7 . The vector of claim 6 , wherein the vector comprises Adeno-associated virus (AAV).
8 . A method of eliciting an immune response in a mammal comprising administering the nanoparticle of claim 3 .
9 . The method of claim 8 , wherein the mammal is a human.
10 . The method of claim 8 , wherein the mammal is a non-human primate.
11 . The method of claim 8 , wherein the mammal is a mouse.
12 . The method of claim 8 , wherein the mammal comprises elements of a human immune system.
13 . The method of claim 8 , wherein the method comprises administering two or more of the nanoparticles.
14 . The method of claim 13 , wherein the two or more nanoparticles are administered sequentially.
15 . The method of claim 13 , wherein the two or more nanoparticles are administered together.
16 . The method of claim 8 , wherein the nanoparticle is administered with an adjuvant.
17 . The method of claim 16 , wherein the adjuvant comprises a lecithin.
18 . The method of claim 17 , wherein the lecithin is (a) combined with an acrylic polymer, (b) in a coated oil droplet in an oil-in-water emulsion or (c) in an acrylic polymer in an oil-in-water emulsion.
19 . The method of claim 16 , wherein the adjuvant comprises alum.
20 . The method of claim 8 , wherein the nanoparticle is fixed.
21 . The method of claim 20 , wherein the nanoparticle is fixed in glutaraldehyde.
22 . The method of claim 8 , wherein the nanoparticle is quenched with glycine.