US 2015/0030627 A1Published application

Trans-complementing, replication deficient lentiviral vectors and methods for making and using them

AssigneeVIRxSYS.CON390

InventorsXiaobin Lu, Boro Dropulic

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Abstract

The present invention relates to multiple novel approaches for the generation of an immune response in an animal, such as a human, using lentivirus-based vector technology. The invention provides for the ability to mimic the efficacy of a live attenuated (LA) vaccine, without exposing the patient to the risk of disease as possible with some LA vaccines. The invention thus provides for systems of complementary conditionally replicating vectors, vectors that produce replication deficient virus like particles, and multi-antigen constructs that target a virus or microbial pathogen. The use of these materials in the practice of the invention permits the generation of robust cellular and humoral responses to the antigens presented thereby.

Claims17

Dependent claims

An immunogenic composition for in vivo administration comprising two or more trans-complementing, replication-defective lentiviral vectors, wherein:

(a) each vector comprises a lentiviral protein coding sequence and one or more heterologous and/or autologous promoters capable of directing expression of the lentiviral protein,
(b) each of the two or more trans-complementing lentiviral vectors replicates only in the presence of the other trans-complementing lentiviral vector(s),
(c) at least one of the two or more trans-complementing lentiviral vectors comprises:
(i) a coding sequence for one or more human immunodeficiency virus (HIV) antigens capable of generating an immune response in a subject, and an autologous and/or a heterologous promoter or promoters capable of directing expression of the one or more HIV antigens,
(ii) a coding sequence for one or more immunomodulatory proteins capable of enhancing an antigen-specific immune response in a subject, and an autologous and/or a heterologous promoter or promoters capable of directing expression of the one or more immunomodulatory proteins, and
(iii) an antiviral agent to prevent recombination between the two or more trans-complementing lentiviral vectors,
wherein the one or more HIV antigens comprise(s) epitopes selected from the group consisting of gag-pol, env, vif, vpr, tat, rev and nef,
and the antiviral agent is selected from the group consisting of targeted antisense sequences, ribozymes and small interfering RNAs (siRNAs) directed to any of the other trans-complementing lentiviral vector(s).

5 more elements

A vaccine composition for in vivo administration comprising two or more trans-complementing, replication-defective lentiviral vectors, wherein:

(a) each vector comprises a lentiviral protein coding sequence and one or more heterologous and/or autologous promoters capable of directing expression of the lentiviral protein,
(b) each of the two or more trans-complementing lentiviral vectors replicates only in the presence of the other trans-complementing lentiviral vector(s),
(c) at least one of the two or more trans-complementing lentiviral vectors comprises:
(i) a coding sequence for one or more human immunodeficiency virus (HIV) antigens capable of generating an immune response in a subject, and an autologous and/or a heterologous promoter or promoters capable of directing expression of the one or more HIV antigens,
(ii) a coding sequence for one or more immunomodulatory proteins capable of enhancing an antigen-specific immune response in a subject, and an autologous and/or a heterologous promoter or promoters capable of directing expression of the one or more immunomodulatory proteins, and
(iii) an antiviral agent to prevent recombination between the two or more trans-complementing lentiviral vectors,
wherein the one or more HIV antigens comprise(s) epitopes selected from the group consisting of gag-pol, env, vif, vpr, tat, rev and nef and the antiviral agent is selected from the group consisting of targeted antisense sequences, ribozymes and small interfering RNAs (siRNAs) directed to any of the other trans-complementing lentiviral vector(s).

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/121,699Filed 8 Oct 2014
Priority: 17 Aug 2006
Published: 29 Jan 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

A61K 39/21
Viral antigens: retroviridae, e.g. equine infectious anemia virus
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
A61P 31/12
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antivirals
A61P 31/18
For RNA viruses: for HIV