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Article: Design, construction, and characterization of a multigenic modified vaccinia ankara candidate vaccine against human immunodeficiency virus type 1 subtype C/B′

TitleDesign, construction, and characterization of a multigenic modified vaccinia ankara candidate vaccine against human immunodeficiency virus type 1 subtype C/B′
Authors
Issue Date2008
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.jaids.com
Citation
Journal Of Acquired Immune Deficiency Syndromes, 2008, v. 47 n. 4, p. 412-421 How to Cite?
AbstractThe rapid spread of HIV-1 underscores the urgent need to develop an effective vaccine. Using modified vaccinia Ankara (MVA) as a vector, we designed and constructed a multigenic candidate vaccine against a recombinant C/B′ subtype of HIV-1 that is dominant in southwest China. Five HIV-1 genes (gag, pol, ΔV2env, tat, and nef) were introduced into 2 separate regions of the MVA genome using modified single- and dual-promoter insertion vectors. Recombinant MVA was selected by immunofluorescence double-staining and foci purification. The end product is a single recombinant MVA, termed ADMVA, that expresses HIV-1 ΔV2Env and fusion proteins Gag-Pol and Nef-Tat. By in vitro analyses, all expected HIV-1 proteins were expressed in infected chicken embryo fibroblasts and various human cell lines. Additionally, 2 sequential intramuscular injections of 10 50% tissue infectious culture dose (TCID50) of ADMVA into BALB/c and B6 × B10 mice elicited broad cell-mediated immune responses against all 5 viral proteins as determined by interferon-γ enzyme immunospot assays. The number of spot-forming cells was in the range of 200 to 800 per million splenocytes, and both CD4 and CD8 T-cell responses were detected. Moreover, high serum titers (>1:20,000) of antibodies against HIV-1 gp120 were also elicited. The magnitude of immune responses correlated with the dose of ADMVA, and the vaccine caused no overt adverse consequences, up to 10 TCID50 per injection. ADMVA has since been advanced into clinical trials. A phase 1 study has been completed, and a prime-boost with ADVAX (see accompanying article) is now underway. © 2008 Lippincott Williams & Wilkins, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/157507
ISSN
2015 Impact Factor: 3.806
2015 SCImago Journal Rankings: 2.434
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, Zen_US
dc.contributor.authorHuang, Yen_US
dc.contributor.authorZhao, Xen_US
dc.contributor.authorBa, Len_US
dc.contributor.authorZhang, Wen_US
dc.contributor.authorHo, DDen_US
dc.date.accessioned2012-08-08T08:50:40Z-
dc.date.available2012-08-08T08:50:40Z-
dc.date.issued2008en_US
dc.identifier.citationJournal Of Acquired Immune Deficiency Syndromes, 2008, v. 47 n. 4, p. 412-421en_US
dc.identifier.issn1525-4135en_US
dc.identifier.urihttp://hdl.handle.net/10722/157507-
dc.description.abstractThe rapid spread of HIV-1 underscores the urgent need to develop an effective vaccine. Using modified vaccinia Ankara (MVA) as a vector, we designed and constructed a multigenic candidate vaccine against a recombinant C/B′ subtype of HIV-1 that is dominant in southwest China. Five HIV-1 genes (gag, pol, ΔV2env, tat, and nef) were introduced into 2 separate regions of the MVA genome using modified single- and dual-promoter insertion vectors. Recombinant MVA was selected by immunofluorescence double-staining and foci purification. The end product is a single recombinant MVA, termed ADMVA, that expresses HIV-1 ΔV2Env and fusion proteins Gag-Pol and Nef-Tat. By in vitro analyses, all expected HIV-1 proteins were expressed in infected chicken embryo fibroblasts and various human cell lines. Additionally, 2 sequential intramuscular injections of 10 50% tissue infectious culture dose (TCID50) of ADMVA into BALB/c and B6 × B10 mice elicited broad cell-mediated immune responses against all 5 viral proteins as determined by interferon-γ enzyme immunospot assays. The number of spot-forming cells was in the range of 200 to 800 per million splenocytes, and both CD4 and CD8 T-cell responses were detected. Moreover, high serum titers (>1:20,000) of antibodies against HIV-1 gp120 were also elicited. The magnitude of immune responses correlated with the dose of ADMVA, and the vaccine caused no overt adverse consequences, up to 10 TCID50 per injection. ADMVA has since been advanced into clinical trials. A phase 1 study has been completed, and a prime-boost with ADVAX (see accompanying article) is now underway. © 2008 Lippincott Williams & Wilkins, Inc.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.jaids.comen_US
dc.relation.ispartofJournal of Acquired Immune Deficiency Syndromesen_US
dc.rightsJournal of Acquired Immune Deficiency Syndromes. Copyright © Lippincott Williams & Wilkins.-
dc.subject.meshAids Vaccines - Administration & Dosage - Genetics - Immunologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCd4-Positive T-Lymphocytes - Cytology - Immunologyen_US
dc.subject.meshCd8-Positive T-Lymphocytes - Cytology - Immunologyen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCloning, Molecularen_US
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Products, Env - Genetics - Immunology - Metabolismen_US
dc.subject.meshGene Products, Gag - Genetics - Immunology - Metabolismen_US
dc.subject.meshGene Products, Nef - Genetics - Immunology - Metabolismen_US
dc.subject.meshGene Products, Pol - Genetics - Immunology - Metabolismen_US
dc.subject.meshGene Products, Tat - Genetics - Immunology - Metabolismen_US
dc.subject.meshGenetic Vectorsen_US
dc.subject.meshHiv Antibodies - Blooden_US
dc.subject.meshHiv-1 - Genetics - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunization - Methodsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshMice, Inbred Strainsen_US
dc.subject.meshRetroviridae Proteins - Genetics - Immunology - Metabolismen_US
dc.subject.meshTransfectionen_US
dc.subject.meshVaccinia Virus - Geneticsen_US
dc.titleDesign, construction, and characterization of a multigenic modified vaccinia ankara candidate vaccine against human immunodeficiency virus type 1 subtype C/B′en_US
dc.typeArticleen_US
dc.identifier.emailChen, Z:zchenai@hkucc.hku.hken_US
dc.identifier.authorityChen, Z=rp00243en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/QAI.0b013e3181651bb2en_US
dc.identifier.pmid18209682-
dc.identifier.scopuseid_2-s2.0-40549088502en_US
dc.identifier.hkuros147735-
dc.identifier.volume47en_US
dc.identifier.issue4en_US
dc.identifier.spage412en_US
dc.identifier.epage421en_US
dc.identifier.isiWOS:000253913000002-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChen, Z=35271180800en_US
dc.identifier.scopusauthoridHuang, Y=7501575029en_US
dc.identifier.scopusauthoridZhao, X=8781942500en_US
dc.identifier.scopusauthoridBa, L=8557032300en_US
dc.identifier.scopusauthoridZhang, W=7409430773en_US
dc.identifier.scopusauthoridHo, DD=7402971998en_US

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