Hetero-oligomeric HIV envelope proteins

An envelope and glycoprotein technology, applied in the field of vaccines, can solve the problems of inducibility and lack

Inactive Publication Date: 2007-12-26
SEATTLE BIOMEDICAL RES INST
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, HxB2-derived gp120 or gp140 immunogens lacking the V1, V2, and V3 regions, or DH12-derived gp160 / gp120 immunogens lacking V1 and V2, or the V1, V2, and V3 regions did not even induce NAbs against corresponding homologous viruses (Kim et al., 2003; Lu et al., 1998)

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0054] This example discloses HIV-1 gp160 heterotrimers comprising at least one monomer deleted from at least one variable loop.

[0055] Our research group has removed the V1, V2, and V3 regions (individually or in combination) of SF 162 Env by mutagenesis (Saunders et al., 2005; Stamatatos and Cheng-Mayer, 1998; Stamatatos et al., 2000; Stamatatos et al., 1998 ). DNA vectors expressing the parental and the modified proteins have been prepared. Homotrimeric gp140 proteins lacking the V2 loop (dV2), V3 loop (dV3), or both V2 and V3 loops (dV2dV3), as well as the parental gp140 (SF 162), have been used as immunogens to induce NAbs in animals (Barnett et al., 2001; Buckner et al., 2004; Cherpelis et al., 2001; Derby et al., manuscript in preparation). A homotrimeric SF162 construct lacking the V1 loop (dV1) has been made (Saunders et al., 2005).

[0056] In this example, the heterotrimer was engineered to contain different SF 162 -derived monomers in the V1, V2, V3 regions. ...

example 2

[0060] This example discloses HIV-1 gp160 heterotrimers comprising at least one monomer from different clades.

[0061] DNA vectors expressing the gp160Env proteins of four clade A envelopes (Q168, Q259, Q461, and Q769) were provided to us by Dr. Julie Overbaugh of FHCRC. Several modifications were introduced into these constructs. The V1 or V2 loops were eliminated using methods similar to those used to eliminate the loops from SF162 Env (Saunders et al., 2005; Stamatatos and Cheng-Mayer, 1998; Stamatatos et al., 2000; Stamatatos et al., 1998). A conserved N-linked glycosylation site (NLGS) was also eliminated from the N-terminal region of V2 (GMV2), and a conserved NLGS was eliminated from the N-terminus of the V3 loop (GMV3). The above modifications have different effects on the functions of the Envs mentioned above. Certain modifications destroy its ability to mediate infection; some attenuate this ability; and others have no effect on it. Using a similar infection meth...

example 3

[0064] This example discloses soluble HIV-1 gp140 heterotrimers comprising at least one more monomer having at least one variable loop deletion.

[0065] One of several methods can be used to prepare soluble gp140 heterotrimers comprising at least one monomer having a variable loop deletion, see Example 1, for example. In one approach, maltose binding protein (MBP) was introduced into the C-terminus of dV3gp140 and a His-tag was introduced into the C-terminus of dV2gp140. First, the sequence of the HCV-3C cleavage site was introduced into the C-terminus of dV3gp140 and dV2gp140. Then, a His tag sequence was introduced into the HCV-3C C-terminus of dV2gp140, and a maltose binding protein (MBP) sequence was introduced into the HCV-3C C-terminus of dV3gp140.

[0066] Addition of the His tag at the HCV-3C C-terminus of dV2gp140 was achieved using Stratagene's site-directed mutagenesis kit. A primer incorporating a His tag immediately downstream of the 12 nucleotide junction regi...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

In one aspect, the invention provides an HIV envelope heterotrimer comprising at least two different Env glycoprotein monomers. In some heterotrimers, at least two Env glycoprotein monomers are from different HIV isolates, for example, different HIV-1 isolates. Heterotrimers may contain Env glycoprotein monomers from HIV isolates belonging to the same Glade or to different clades or both. At least one of the Env glycoprotein monomers in a heterotrimer of the invention may be modified in a way that alters its amino acid composition. In another aspect, the invention provides methods for inducing an immune response in a vertebrate host against HIV or an HIV-infected cell, comprising administering to a vertebrate host a prophylactically or therapeutically effective amount of a composition comprising an HIV envelope heterotrimer.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 60 / 640,329, filed December 29, 2004, which is incorporated herein by reference. [0003] Statement of Government Licensing Rights [0004] The U.S. Government has a license in this invention for a fee and, in certain instances, to require the patentee to license the patentee to others under reasonable terms issued by the National Institutes of Health under Grant Number No. Available in RO1AI047708. field of invention [0005] The present invention relates to recombinant hybrid oligomeric human immunodeficiency virus (HIV) envelope proteins and their use, eg, as vaccines. Background of the invention [0006] It is increasingly evident that an effective immunization approach against HIV should induce neutralizing antibodies (NAbs) and cell-mediated antiviral responses. Although the protective role of newly formed neutralizing antibody responses ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/16A61K39/21
CPCA61K2039/57C12N2740/16122A61K39/00C07K14/005A61P31/18
Inventor L·斯塔马塔托斯
Owner SEATTLE BIOMEDICAL RES INST
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap