Methods and compositions for heterologous repRNA immunizations

Patent metadata

Field	Value
Publication number	US-11964007-B2
Application number	US-202117645556-A
Country	US
Kind code	B2
Filing date	Dec 22, 2021
Priority date	Jul 28, 2017
Publication date	Apr 23, 2024
Grant date	Apr 23, 2024

Abstract

Compositions and methods are described for inducing an immune response against an immunogen in humans. The induced immune response is obtained by administering a heterologous prime-boost combination of an in vitro transcribed (IVT) self-replicating RNA (repRNA) and an adenovirus vector. The compositions and methods can be used to provide a protective immunity against a disease, such as a viral infection or a cancer, in humans.

First claim

The invention claimed is:

1. A method of inducing an immune response in a human subject in need thereof, the method comprising:
a. administering to the human subject a first composition comprising an immunologically effective amount of an in vitro transcribed (IVT) self-replicating RNA (repRNA) comprising a first polynucleotide encoding a first antigenic protein or an immunogenic polypeptide thereof, together with a pharmaceutically acceptable carrier, wherein the IVT repRNA is formulated into a non-virion particle, and
b. administering to the subject a second composition comprising an immunologically effective amount of a recombinant human adenovirus serotype 26 (Ad26) vector or a recombinant human adenovirus serotype 35 (Ad35) vector comprising a second polynucleotide encoding a second antigenic protein or an immunogenic polypeptide thereof, together with a pharmaceutically acceptable carrier,

to thereby obtain an induced immune response in the human subject, wherein the first or second antigenic protein is derived from an Influenza virus, and wherein the first and second antigenic proteins share at least one antigenic determinant, and one of the compositions is a priming composition and the other composition is a boosting composition.

2. The method according to claim 1 , wherein the composition comprising the IVT repRNA is the priming composition and the composition comprising the adenovirus vector is the boosting composition.

3. The method according to claim 1 , wherein the composition comprising the adenovirus vector is the priming composition and the composition comprising the IVT repRNA is the boosting composition.

4. The method according to claim 1 , wherein the induced immune response comprises an induced antibody immune response against the at least one antigenic determinant shared by the first and second antigenic proteins in the human subject.

5. The method according to claim 1 , wherein the induced immune response comprises an induced cellular immune response against the at least one antigenic determinant shared by the first and second antigenic proteins in the human subject.

6. The method according to claim 1 , wherein the induced immune response provides a protective immunity to the human subject against a disease related to at least one of the first and second antigenic proteins.

7. The method according to claim 1 , wherein the IVT repRNA is a Venezuelan equine encephalitis (VEE) virus-based repRNA.

8. The method according to claim 1 , wherein the boosting composition is administered 1-52 weeks after the priming composition is administered.

9. The method according to claim 1 , wherein the boosting composition is administered at least 1 week after the priming composition is administered.

10. The method according to claim 1 , wherein the first and second antigenic proteins are identical.

11. A combination for inducing an immune response in a human subject, comprising:
a. a first composition comprising an immunologically effective amount of an IVT repRNA comprising a first polynucleotide encoding a first antigenic protein or an immunogenic polypeptide thereof, together with a pharmaceutically acceptable carrier, wherein the IVT repRNA is formulated into a non-virion particle, and
b. a second composition comprising an immunologically effective amount of a recombinant human adenovirus serotype 26 (Ad26) vector or a recombinant human adenovirus serotype 35 (Ad35) vector comprising a second polynucleotide encoding a second antigenic protein or an immunogenic polypeptide thereof, together with a pharmaceutically acceptable carrier,

wherein the first or second antigenic protein is derived from an Influenza virus, and wherein the first and second antigenic proteins share at least one antigenic determinant, and one of the compositions is a priming composition and the other composition is a boosting composition.

12. The combination of claim 11 , wherein the composition comprising the IVT repRNA is the priming composition and the composition comprising the adenovirus vector is the boosting composition.

13. The combination of claim 11 , wherein the composition comprising the adenovirus vector is the priming composition and the composition comprising the IVT repRNA is the boosting composition.

14. The combination of claim 11 , wherein the first and second antigenic proteins are identical.

15. The combination of claim 11 , wherein the IVT repRNA is a VEE virus-based repRNA.

16. The method of claim 1 , wherein the IVT repRNA is formulated into a lipid nanoparticle.

17. The combination of claim 11 , wherein the IVT repRNA is formulated into a lipid nanoparticle.

Assignees

• Janssen Vaccines & Prevention Bv
• Massachusetts Inst Technology

Inventors

• Vogels Ronald
• Van Der Neut Kolfschoten Marijn
• Irvine Darrell J
• Weiss Ron
• Porter Ely Blanton
• Melo Mariane Bandeira
• Kitada Tasuku

Classifications

• A61K39/12 Primary

  Viral antigens · CPC title

• C12N15/86

  Viral vectors · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K2039/545

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

• C12N2760/18534

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