HIV-1 Env fusion peptide immunogens and their use

Patent metadata

Field	Value
Publication number	US-11602559-B2
Application number	US-201716338964-A
Country	US
Kind code	B2
Filing date	Oct 3, 2017
Priority date	Oct 3, 2016
Publication date	Mar 14, 2023
Grant date	Mar 14, 2023

Abstract

Embodiments of immunogens based on the HIV-1 Env fusion peptide and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to generate an immune response to HIV-1 Env in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

First claim

It is claimed:

1. An immunogen, comprising an HIV-1 Env fusion peptide conjugated to a carrier protein by a heterologous linker, wherein:
the HIV-1 Env fusion peptide consists of the amino acid sequence set forth as AVGIGAVF (residues 1-8 of SEQ ID NO: 1);
the carrier is a tetanus toxoid heavy chain C fragment; and
the immunogen elicits a neutralizing immune response to HIV-1 in a subject.

2. The immunogen of claim 1 , wherein:
the HIV-1 Env fusion peptide is conjugated to the carrier by a linker between a lysine residue on the carrier and a heterologous cysteine residue fused to the C-terminal residue of the HIV-1 Env fusion peptide.

3. The immunogen of claim 1 , wherein the average molar ratio of the HIV-1 Env fusion peptide to the carrier in the immunogenic conjugate is between about 1:1 and 1000:1.

4. The immunogen of claim 1 , wherein the immunogen specifically binds to a VRC34 antibody.

5. An immunogenic composition comprising the immunogen of claim 1 , and a pharmaceutically acceptable carrier.

6. The immunogenic composition of claim 5 , further comprising an adjuvant.

7. The immunogenic composition of claim 6 , wherein the adjuvant is a saponin adjuvant or a carbomer-lecithin adjuvant.

8. A method for generating an immune response to HIV-1 in a subject, comprising administering to the subject an effective amount of the immunogen of claim 1 to generate the immune response.

9. The method of claim 8 , wherein generating the immune response to HIV-1 in the subject comprises a prime-boost immunization comprising administering the immunogen to the subject one or more times followed by administering a soluble HIV-1 envelope trimer to the subject one or more times.

10. The method of claim 9 , wherein the soluble HIV-1 envelope trimer is stabilized in a prefusion conformation by one or more amino acid substitutions.

11. The method of claim 9 , wherein the soluble HIV-1 envelope trimer comprises one or more amino acid substitutions to remove an N-linked glycan sequon at one or more of HXB2 positions N88, N230, N241, and N611.

12. The method of claim 8 , wherein the immune response treats or inhibits HIV-1 infection in the subject.

13. The method of claim 8 , wherein generating the immune response inhibits HIV-1 replication in the subject.

14. The immunogen of claim 1 , wherein the linker is a Sulfo-SIAB linker.

15. The immunogen of claim 1 , wherein the tetanus toxoid heavy chain C fragment comprises the amino acid sequence set forth as SEQ ID NO: 198.

16. The immunogen of claim 1 , wherein the carrier is tetanus toxoid heavy chain C fragment comprising the amino acid sequence set forth as SEQ ID NO: 198, and the linker is a Sulfo-SIAB linker.

Assignees

• Us Health

Inventors

• Kwong Peter
• Kong Rui
• Zhou Tongqing
• Mascola John
• Xu Kai
• Cheng Cheng
• Chuang Gwo-Yu
• Liu Kevin
• Zhang Baoshan
• Ou Li
• Kong Wing-Pui

Classifications

• C07K16/1145 Primary

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · CPC title

• A61K2039/6037

  Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT] · CPC title

• C12N2740/16171

  Demonstrated in vivo effect · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K39/12

  Viral antigens · CPC title