Ferritin nanoparticle displaying an hiv trimer

Patent metadata

Field	Value
Publication number	US-2021363194-A1
Application number	US-201917255408-A
Country	US
Kind code	A1
Filing date	Jun 5, 2019
Priority date	Jun 5, 2018
Publication date	Nov 25, 2021
Grant date	—

Abstract

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.

First claim

What is claimed is:

1 . A synthetic peptide which comprises a glycosylated Env peptide of HIV and a support peptide, wherein the synthetic peptide is 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.

2 . The peptide of claim 1 , wherein the Env peptide is glycosylated with oligomannose.

3 . The peptide of claim 1 , wherein the support peptide comprises at least 25 contiguous amino acids that are at least 80% identical to a bacterial ferritin, a plant ferritin, an algal ferritin, an insect ferritin, a fungal ferritin or a mammalian ferritin.

4 . The peptide of claim 3 , wherein the support peptide comprises at least 25 contiguous residues that are at least 80% identical to Pyrococcus furioso ferritin (SEQ ID NO:5)

5 . The peptide of claim 3 , wherein the ferritin comprises at least 25 contiguous residues that are at least 80% identical to Helicobacter pylori ferritin (SEQ ID NO:6).

6 . The peptide of claim 3 , wherein the ferritin comprises at least 25 contiguous residues that are at least 80% identical to human ferritin (SEQ ID NO:7).

7 . The peptide of claim 1 , wherein the support peptide comprises lumazine synthase (LS) or a fragment thereof.

8 . The peptide of any one of claims 1 to 7 , which comprises BG505_SOSIP_MD39_JD6_m (SEQ ID NO:1), 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).

9 . A nanoparticle which comprises a plurality of peptides of any one of claims 1 - 8 .

10 . A nucleic acid encoding the peptide of any one of claims 1 - 8 .

11 . A vector comprising a regulatory element operable in a eukaryotic cell operably linked to the nucleic acid of claim 10 .

12 . The vector of claim 11 , wherein the vector comprises a viral vector.

13 . The vector of claim 12 , wherein the vector comprise AAV.

14 . A method of eliciting an immune response in a mammal comprising administering the nanoparticle of claim 9 .

15 . A method of stimulating of a broadly neutralizing HIV antibody (bnAb) in a mammal comprising administering the nanoparticle of claim 9 .

16 . The method of claim 15 , which comprises stimulating a germline precursor of a bnAb.

17 . The method of any one of claim 10 or 15 , wherein the mammal is a human.

18 . The method of any one of claim 10 or 15 , wherein the mammal is a non-human primate.

19 . The method of any one of claim 10 or 15 , wherein the mammal is a mouse.

20 . The method of any one of claim 10 or 15 , wherein the mammal comprises elements of a human immune system.

21 . The method of any one of claims 14 to 20 , wherein the method comprises administering two or more nanoparticles comprising two or more peptides of any one of claims 1 - 8 .

22 . The method of claim 21 , wherein the peptides or nanoparticles are administered sequentially.

23 . The method of claim 21 , wherein the peptides or nanoparticles are administered together.

24 . The method of any one of claim 14 or 15 , wherein the nanoparticle is administered with an adjuvant.

25 . The method of claim 24 , wherein the adjuvant comprises a lecithin.

26 . The method of claim 25 , 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.

27 . The method of claim 25 , wherein the adjuvant is ISCOMATRIX or Adjuplex.

28 . The method of claim 24 , wherein the adjuvant comprises alum.

29 . The method of any one of claims 14 to 28 , wherein the peptide or nanoparticle is fixed.

30 . The method of claim 29 , wherein the peptide or nanoparticle is fixed in glutaraldehyde.

31 . The method of any one of claims 14 to 30 , wherein the peptide or nanoparticle is quenched with glycine.

32 . A method of improving the immunogenicity of a peptide which comprises a glycosylated Env peptide of HIV and a support peptide, which comprises increasing the glycan density of the peptide.

33 . The method of claim 32 , wherein the peptide is comprises by a nanoparticle.

Assignees

• Int Aids Vaccine Initiative
• Scripps Research Inst
• Massachusetts Inst Technology

Inventors

• Tokatlian Talar
• Read Benjamin J
• Kulp Daniel W
• Menis Sergey
• Steichen Jon M
• Schief William R
• Irvine Darrell J

Classifications

• C07K14/162 Primary

  env, e.g. gp160, gp110/120, gp41, V3, peptid T, CD4-Binding site · CPC title

• C12N2740/16022

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2740/16134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title