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Methods and compositions for inducing an immune response using conserved element constructs

Inactive Publication Date: 2018-12-06
US DEPT OF HEALTH & HUMAN SERVICES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a method for improving the immune response to a vaccine by using a combination of nucleic acid constructs and a boosting immunogen. The method focuses the immune response on the highly conserved epitopes of the virus or immunogen, resulting in better breadth, magnitude, and quality of immune responses. The boosting step involves co-administration of a vaccine expressing conserve element polypeptides (CE immunogens) with a full-length molecule. The CE immunogens are engineered to express different forms of the polypeptides and can be directed to specific cellular compartments or targeted for degradation. The technical effect of this method is superior immune responses to vaccines, especially in cases where the immunogen is not very effective on its own.

Problems solved by technology

Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV.

Method used

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  • Methods and compositions for inducing an immune response using conserved element constructs
  • Methods and compositions for inducing an immune response using conserved element constructs
  • Methods and compositions for inducing an immune response using conserved element constructs

Examples

Experimental program
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Effect test

example 1

Illustration of Enhanced Immune Responses Obtained with CE Construct Prime Followed by CE and Full-Length Polypeptides as Boost

[0257]This example evaluated prime-boost combination vaccines to increase breadth of immunity. In addition to the CE prime-full length molecule boost, it was found that using a boost involving co-delivery of CE and full-length molecule resulted in significantly further improved breadth of the responses. This boost further elicited higher levels of cytotoxic T cells focusing the immune responses to the highly conserved epitopes.

[0258]Method: this study was performed using a simian immunodeficiency virus (SIV) derived conserved element pDNA vaccine that was designed from the SIV p27gag capsid protein by analogy to an HIV CE vaccine. The SIV p27gag is the proteolytic processing product derived from the full length SIV p57gag protein. Seven highly conserved elements were identified within the p27gag capsid protein by (i) analogy to HIV CE sequences and (ii) sequ...

example 2

Env DNA Vaccination Induces Cross-Clade Specific Cellular Immune Responses in Mice

Result:

Conserved Element DNA Vaccines

[0270]A set of conserved elements (CE) was identified in the HIV Env protein (FIG. 9). This example describes the identification of 12 conserved elements in HIV Env of 11, 14, 21, 15, 23, 21, 13, 12, 14, 43, 20, and 13 AA in length (FIG. 10). Each CE segment is separated by linkers 3 amino acids in length, composed of alanine and some of which also contain a valine, glutamic acid, lysine, aspartic acid, phenylalanine or glycine, designed to facilitate processing of the protein. Expression-optimized synthetic Env-CE1 and Env-CE2 genes were inserted into an eukaryotic expression vector pCMVkan between the human CMV promoter and bovine growth hormone poly A signal. pCMVkan is optimized for optimal growth in bacteria (kanR) and expression of the insert in mammalian cells.

[0271]Regions for inclusion / exclusion from the vaccine were selected based on whether immune respons...

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Abstract

The invention provides methods and compositions for eliciting broad immune responses to HIV envelope proteins. The methods include use of nucleic acids constructs that encode conserved elements of HIV Env to induce immune responses.

Description

CROSS-REFERENCE TO RELATING APPLICATIONS[0001]This application claims priority benefit of U.S. Provisional Application No. 62 / 161,123, filed May 13, 2015; and U.S. Provisional Application No. 62 / 241,599, filed Oct. 14, 2015; each of which applications is herein incorporated by reference.BACKGROUND OF THE INVENTION[0002]Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV. A vaccine that can induce cross-clade specific immune responses is sought. One approach to achieving robust cross-clade immune responses is the use of conserved element (CE) vaccines (see, e.g., WO 2012 / 062873 and WO 2013 / 131099) that can serve as a “universal” vaccine in that it is able to induce immune responses to most or all circulating strains of a virus. It was additionally determined that improved immune responses to highly conserved regions were obtained using a prime-boost vaccine regimen that included CE prime followed by boost with a vector expressi...

Claims

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Application Information

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IPC IPC(8): C07K14/005A61K9/00A61K39/21A61K39/39C07K14/535
CPCC07K14/005A61K9/0009A61K9/0019A61K39/21A61K39/39C07K14/535C12N2740/16271C12N2740/16234C12N2740/16222A61K2039/545A61K2039/53A61K2039/575A61K2039/54C12N2740/16134C12N2740/16171C12N2740/16122C07K2319/02A61K2039/55522A61K2039/55561C07K14/161A61K2039/572A61K39/00
Inventor FELBER, BARBARA K.PAVLAKIS, GEORGE N.MULLINS, JAMES I.VALENTIN, ANTONIOMANOCHEEWA, SIRIPHAN
Owner US DEPT OF HEALTH & HUMAN SERVICES
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