Improvments in or relating to immune responses to HIV

An immune response, immunogen technology, applied in the field of immunogen, can solve the problems of difficulty and difficulty in neutralizing primary isolates

Inactive Publication Date: 2003-08-06
MEDICAL RESEARCH COUNCIL +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this has proven to be extremely difficult (Heilman and Baltimore 1998 Nat. Med. 4(4Suppl.) 532-534)
Neutralization of primary isolates was extremely difficult ( Trkola et al., 1998 J. Virol. 72, 1876-1885; Haynes 1996 Lancet 34, 933-937)

Method used

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  • Improvments in or relating to immune responses to HIV
  • Improvments in or relating to immune responses to HIV
  • Improvments in or relating to immune responses to HIV

Examples

Experimental program
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Embodiment Embodiment 1

[0065] This example relates to an immunogen used in a vaccine that is mainly used to induce + Helper T lymphocytes and CD8 + Cellular immune response mediated by synergy of effector T lymphocytes. The immunogen designated HIVA (Hanke & McMichael Nat. Med. 6, 951-955) has been designed for a Phase III efficacy clinical trial in Nairobi, Kenya. Figure 1A is a schematic diagram of some immunogens including HIVA. HIVA is derived from the sequence of HIV-1 clade A, the most dominant HIV clade in the Nairobi region and consists of approximately 73% gag protein fused to a string of 25 partially overlapping CTL epitopes. The gag domain of HIVA contains p24 and p17 in reverse order to the viral gag p17-p24-p15 polyprotein. This rearrangement prevents myristoylation of the N-terminus of p17, which can direct recombinant proteins to the cell membrane, thus preventing efficient degradation of the peptides necessary for class I major histocompatibility complex (MHC) presentation.

[00...

Embodiment 2

[0085] Other nucleic acid constructs encoding HIVA-based polyprotein immunogens are prepared. These other constructs and the immunogens encoded by them are referred to as HIVTA and HIVAeT, as shown in Figure 1A. Also shown is the construct / immunogen called PPA. The relevant DNA / amino acid sequences are shown in Figures 6A / B-8A / B, respectively, although Figure 7A shows only a part of the amino acid sequence in HIVAeT (attributable to tat), an additional part of the sequence in HIVTA. (Note that the sequences of the HindIII and XbaI sites at the 5' and 3' ends of the DNA sequence are not shown in Figures 6B, 7B and 8B). This construct was prepared by a method similar to that described previously for the construction of HIVA.

[0086] HIVTA and HIVAeT are designed on the same principles as HIVA, but additionally include the HIV-1 clade A tat sequence expressed as part of a protein fused to gag and a polyepitopic synthetic polypeptide (in HIVTA, the tat sequence is between gag a...

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Abstract

Disclosed is an immunogen in sterile form suitable for administration to a human subject, the immunogen comprising: at least a portion of the gag protein of HIV, said gag protein being from an HIV clade or having a consensus sequence for one or more HIV clades, and comprising at least parts of p17 and p24; and a synthetic polypeptide comprising a plurality of amino acid sequences, each sequence comprising a human CTL epitope of an HIV protein, and wherein a plurality of HIV proteins are represented in the synthetic polypeptide, said CTL epitopes being selected to stimulate an immune response to one or more HIV clades of interest.

Description

field of invention [0001] The present invention relates to an immunogen designed to elicit an anti-HIV immune response (particularly a cell-mediated response) in a human subject, a nucleic acid molecule encoding the immunogen, comprising said immunogen and / or compositions of said nucleic acid molecules, and methods of inducing an anti-HIV immune response (particularly a cell-mediated response) in a human subject. Background of the invention [0002] To develop an effective human immunodeficiency virus (HIV) vaccine is one of the main purposes of current research on acquired immunodeficiency syndrome (AIDS). Despite advances in HIV infection prevention and potent drug combination treatments, an estimated 16,000 people are still infected every day. More than 90% of new infections occur in developing countries, where the latest medical advances are not yet available or affordable. The best hope for these countries is the development of an effective, accessible HIV vaccine. C...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/09A61K38/00A61K39/00A61K39/02A61K39/21A61K48/00A61P31/18C07K14/155C07K14/16C12N1/21C12N7/00
CPCC12N2740/16222C07K2319/00A61K38/00A61K39/00C07K14/005A61P31/18
Inventor T·翰克A·J·麦克迈克尔
Owner MEDICAL RESEARCH COUNCIL
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