Ferritin nanoparticle displaying an HIV trimer

Patent metadata

Field	Value
Publication number	US-12570701-B2
Application number	US-201917255408-A
Country	US
Kind code	B2
Filing date	Jun 5, 2019
Priority date	Jun 5, 2018
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

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 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.

Assignees

• Int Aids Vaccine Initiative Inc
• 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

• C12N2740/16134

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

• C12N2740/16034

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

• C12N2740/16022

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

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K2039/6031

  Proteins · CPC title