US 8,673,316 B2Granted

Avirulent, immunogenic flavivirus chimeras

AssigneesThe United States of America as represented by the Secretary of the Department of Health and Human Services, Centers for Disease Control and Prevention, Mahidol University

InventorsRichard M. Kinney, Claire Y. H. Kinney, Duane J. Gubler, Siritorn Butrapet, Natth Bhamarapravati

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Abstract

Chimeric flaviviruses that are avirulent and immunogenic are provided. The chimeric viruses are constructed to contain amino acid mutations in the nonstructural viral proteins of a flavivirus. Chimeric viruses containing the attenuation-mutated nonstructural genes of the virus are used as a backbone into which the structural genes of a second flavivirus strain are inserted. These chimeric viruses elicit pronounced immunogenicity yet lack the accompanying clinical symptoms of viral disease. The attenuated chimeric viruses are effective as immunogens or vaccines and may be combined in a pharmaceutical composition to confer simultaneous immunity against several strains of pathogenic flaviviruses.

Claims27

Dependent claims

A tetravalent Dengue virus immunogenic composition comprising:

a first nucleic acid molecule comprising an attenuated Dengue-2 virus;
a second nucleic acid molecule comprising a chimeric Dengue-2 virus/Dengue-1 virus comprising a nucleic acid sequence encoding at least one non-structural protein from an attenuated Dengue-2 virus strain and a nucleic acid sequence encoding at least one structural protein from a Dengue-1 virus;
a third nucleic acid molecule comprising a chimeric Dengue-2 virus/Dengue-3 virus comprising a nucleic acid sequence encoding at least one non-structural protein from an attenuated Dengue-2 virus and at least one structural protein from a Dengue-3 virus;
and
a fourth nucleic acid molecule comprising a chimeric Dengue-2 virus/Dengue-4 virus comprising a nucleic acid sequence encoding at least one non-structural protein from an attenuated Dengue-2 virus strain and at least one structural protein from a Dengue-4 virus.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/212,845Filed 18 Aug 2011 · continuation
Priority: 16 Feb 2000
Published: US 2012/0014981 A119 Jan 2012
Granted: 18 Mar 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

A61K 39/12
Medicinal preparations containing antigens or antibodies: viral antigens
A61K 39/295
Viral antigens: polyvalent viral antigens ; Mixtures of viral and bacterial antigens
A61P 31/12
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antivirals
A61P 31/14
Antivirals: for RNA viruses

Family

Application60/182,829Us provisional application · filed 16 Feb 2000
PCT/US01/05142Parent of this division · filed 16 Feb 2001
Application11/506,251Parent of this division · filed 18 Aug 2006
Application12/607,746Parent of this continuation · filed 28 Oct 2009
US 2012/0014981 A1Pre-grant publication · published 19 Jan 2012
US 8,025,887 B2Parent of this continuation
US 7,641,909 B2Parent of this division
Application12/607,746Parent of this division
Application10/204,252Parent of this division
US 7,094,411 B2Parent of this division
US 2006/0062803 A1Published application
US 2009/0010961 A1Published application
US 2010/0255030 A1Published application
US 8,673,316 B2This patent

From the US filing history. Foreign family members aren’t listed.