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Strong immune induction by using combination of adenovirus type-5/type-35 vector and vaccinia virus mva vector

A technology of recombinant virus vector and adenovirus, which is applied in the field of anti-HIV drugs, can solve the problems of inability to produce strong immune induction, inability to administer large amounts of drugs, and strong liver toxicity

Inactive Publication Date: 2009-03-25
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, among the vaccines known in the world, the vaccine obtained by using the adenovirus type 5 vector is a very strong immunogenic vaccine, but there are the following problems: many patients have neutralizing antibodies against the adenovirus type 5, and in In such patients, strong immune induction cannot be produced; and since adenovirus type 5 is very harmful to the liver, it cannot be administered in large quantities (Non-Patent Document 1)
[0008] However, there are no reports of combinations of different recombinant viral vector vaccines

Method used

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  • Strong immune induction by using combination of adenovirus type-5/type-35 vector and vaccinia virus mva vector
  • Strong immune induction by using combination of adenovirus type-5/type-35 vector and vaccinia virus mva vector
  • Strong immune induction by using combination of adenovirus type-5/type-35 vector and vaccinia virus mva vector

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Experimental program
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Embodiment 1

[0075] Experimental methods and materials

[0076] recombinant vector

[0077] The recombinant virus obtained by substituting the cilia of non-propagating adenovirus type 5 lacking E1 and E3 with the cilia derived from adenovirus type 35, and introducing the rev gene and env gene of HIVIIIB, which is an HIV strain of subtype B, was used Ad generation kit (Avior Therapeutics Inc., Seattle, WA, USA) (Shayakhmetov D.M., et al., J. Virol. 2000; 74:2567-2583) was constructed. Simply stated, will contain the CAG promoter-HIV IIIB A 5.2k bp Sall / Pstl fragment of rev / envgp160-polyA was isolated from pCAGrev / env (Jounai N. et al., J. Gene Med. 2003; 5:609-617). The shuttle plasmid (pLHSP) containing the 22-342 site, 3523-5790 site of adenovirus type 5 (Ad5), E. coliori, and the ampicillin resistance gene was obtained from Avior Therapeutics Inc. (Seattle, WA, USA). The blunt-ended 5.2 kbp fragment was subcloned in the blunt-ended EcoRI site of pLHSP to generate the pLHSP-HIV shuttle...

Embodiment 2

[0103] recombinant vector

[0104]The preparation method of the MVA vaccine that reports SIVenv and SIVgag: Insert SIVenv (GenBankNo.AAA47632.1) and SIVgag genes (GenBank No.AAA47637.1) (Dr.ThomasC Friedrich, Wisconsin national Primate Research Center, Madison, WI53706 USA provides) To the SalI / PstI site of the MVA virus shuttle vector (pLW44) (provided by Dr. Bernard Moss, LVD, NIAID, NIH, Bethesda, MD 20892-0445 USA. PNAS101:6641-46, 2004). The successfully inserted vector was introduced into BHK21 cells (American Type culture Collection, The Global Bioresource Center, Manassas, VA20108, USA) infected with wild strain MVA (provided by Dr. Bernard Moss) with lipofbctamin (Invitrogen, Carisbad, CA92008, USA) . The recombinant MVA virus was refined with sucrose (Sucrose) (Wako, Tokyo, Japan). Report the making method of the Ad5 / 35 vector of SIVenv and SIVgag: use SIVenv (GenBank No.AAA47632.1) and SIVgag gene (GenBank No.AAA47637.1) (Dr.Thomas C Friedrich, Wisconsin national ...

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Abstract

Disclosed is an effective and inexpensive anti-HIV agent. The anti-HIV agent comprises a combination of a recombinant viral vector having the structural gene of HIV inserted into a chimeric virus and a recombinant viral vector having the structural gene of HIV inserted into a modified vaccinia virus Ankara, wherein the chimeric virus is prepared by substituting a fiber in an adenovirus type-5 by a fiber derived from an adenovirus type-35.

Description

technical field [0001] The present invention relates to an anti-HIV drug, which is used in combination with a recombinant virus vector vaccine obtained by using chimeric adenovirus type 5 / 35 vector and a recombinant virus vector vaccine obtained by utilizing poxvirus MVA vector. Background technique [0002] More than 20 years have passed since the human immunodeficiency virus (HIV) was identified, but no perfect treatment has yet been established. [0003] After the initial azide thymidine (AZT) was developed as an anti-HIV drug, new anti-HIV drugs were gradually developed. In 1995, HAART (Highly Active Anti -retroviral Therapy), which has sharply reduced the number of deaths from AIDS in advanced countries. [0004] However, in this treatment method, if the administration of the anti-HIV drug is discontinued, HIV re-proliferates after 2 to 3 weeks. Moreover, drug-resistant viruses will also gradually emerge, and newer anti-HIV drugs will be needed to deal with these prob...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K31/7088A61K35/76A61K39/00A61K39/21A61K45/00A61P31/18A61P37/04A61P43/00
CPCC12N2740/15034C12N2710/24143A61K2039/5256C12N2740/16234A61K39/21C12N2710/10345C12N15/86A61K39/12A61P31/12A61P31/18A61P37/04A61P43/00
Inventor 奥田研尔岛田胜
Owner ZHEJIANG HISUN PHARMA CO LTD
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