Evaluation of envelope vaccines derived from the South African subtype C human immunodeficiency virus type 1 TV1 strain

dc.contributor.authorLian Y.
dc.contributor.authorSrivastava I.
dc.contributor.authorGomez-Roman V.R.
dc.contributor.authorZur Megede J.
dc.contributor.authorSun Y.
dc.contributor.authorKan E.
dc.contributor.authorHilt S.
dc.contributor.authorEngelbrecht S.
dc.contributor.authorHimathongkham S.
dc.contributor.authorLuciw P.A.
dc.contributor.authorOtten G.
dc.contributor.authorUlmer J.B.
dc.contributor.authorDonnelly J.J.
dc.contributor.authorRabussay D.
dc.contributor.authorMontefiori D.
dc.contributor.authorVan Rensburg E.J.
dc.contributor.authorBarnett S.W.
dc.identifier.citationJournal of Virology
dc.description.abstractHuman immunodeficiency virus type 1 (HIV-1) subtype C infections are on the rise in Sub-Saharan Africa and Asia. Therefore, there is a need to develop an HIV vaccine capable of eliciting broadly reactive immune responses against members of this subtype. We show here that modified HIV envelope (env) DNA vaccines derived from the South African subtype C TV1 strain are able to prime for Immoral responses in rabbits and rhesus macaques. Priming rabbits with DNA plasmids encoding V2-deleted TV1 gp140 (gp140TV1ΔV2), followed by boosting with oligomeric protein (o-gp140TV1ΔV2) in MF59 adjuvant, elicited higher titers of env-binding and autologous neutralizing antibodies than priming with DNA vaccines encoding the full-length TV1 env (gp160) or the intact TV1 gp140. Immunization with V2-deleted subtype B SF162 env and V2-deleted TVl env together using a multivalent vaccine approach induced high titers of oligomeric env-binding antibodies and autologous neutralizing antibodies against both the subtypes B and C vaccine strains, HIV-1 SF162 and TV1, respectively. Low-level neutralizing activity against the heterologous South African subtype C TV2 strain, as well as a small subset of viruses in a panel of 13 heterologous primary isolates, was observed in some rabbits immunized with the V2-deleted vaccines. Immunization of rhesus macaques with the V2-deleted TV1 DNA prime/protein boost also elicited high titers of env-binding antibodies and moderate titers of autologous TV1 neutralizing antibodies. The pilot-scale production of the various TV1 DNA vaccine constructs and env proteins described here should provide an initial platform upon which to improve the immunogenicity of these subtype C HIV envelope vaccines. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
dc.subjectbinding protein
dc.subjectDNA vaccine
dc.subjectHuman immunodeficiency virus vaccine
dc.subjectneutralizing antibody
dc.subjectunclassified drug
dc.subjectvirus envelope protein
dc.subjectvirus envelope vaccine
dc.subjectanimal cell
dc.subjectantibody response
dc.subjectantibody titer
dc.subjectcytotoxic T lymphocyte
dc.subjecthuman cell
dc.subjectHuman immunodeficiency virus 1
dc.subjectHuman immunodeficiency virus 1 subtype c
dc.subjectimmune response
dc.subjectpriority journal
dc.subjectSouth Africa
dc.subjectvirus envelope
dc.subjectvirus isolation
dc.subjectvirus strain
dc.subjectAIDS Vaccines
dc.subjectAmino Acid Sequence
dc.subjectDrug Evaluation, Preclinical
dc.subjectGene Deletion
dc.subjectGene Products, env
dc.subjectHIV Antibodies
dc.subjectHIV Envelope Protein gp160
dc.subjectHIV Infections
dc.subjectImmunization, Secondary
dc.subjectInjections, Intramuscular
dc.subjectMacaca mulatta
dc.subjectMolecular Sequence Data
dc.subjectNeutralization Tests
dc.subjectSequence Alignment
dc.subjectSouth Africa
dc.subjectVaccines, DNA
dc.subjectHuman immunodeficiency virus 1
dc.subjectMacaca mulatta
dc.subjectOryctolagus cuniculus
dc.titleEvaluation of envelope vaccines derived from the South African subtype C human immunodeficiency virus type 1 TV1 strain

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