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dc.contributor.author Graham, BS
dc.contributor.author McElrath, MJ
dc.contributor.author Keefer, MC
dc.contributor.author Rybczyk, K
dc.contributor.author Berger, D
dc.contributor.author Weinhold, KJ
dc.contributor.author Ottinger, J
dc.contributor.author Ferarri, G
dc.contributor.author Montefiori, DC
dc.contributor.author Stablein, D
dc.contributor.author Smith, C
dc.contributor.author Ginsberg, R
dc.contributor.author Eldridge, J
dc.contributor.author Duerr, A
dc.contributor.author Fast, P
dc.contributor.author Haynes, BF
dc.contributor.author AIDS Vaccine Evaluation Group
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:33Z
dc.date.issued 2010-08-10
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20706632
dc.identifier.citation PLoS One, 2010, 5 (8), pp. e11995 - ?
dc.identifier.uri http://hdl.handle.net/10161/4559
dc.description.abstract BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886.
dc.format.extent e11995 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0011995
dc.subject Abscess
dc.subject Adolescent
dc.subject Adult
dc.subject Antibody Formation
dc.subject Female
dc.subject Freund's Adjuvant
dc.subject HIV-1
dc.subject Humans
dc.subject Immunization
dc.subject Male
dc.subject Mannitol
dc.subject Middle Aged
dc.subject Oleic Acids
dc.subject Peptides
dc.subject T-Lymphocytes
dc.subject Vaccines, Subunit
dc.subject Young Adult
dc.title Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-8-10 en_US
duke.description.endpage e11995 en_US
duke.description.issue 8 en_US
duke.description.startpage e11995 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20706632
pubs.issue 8
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Global Health Institute
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Duke Human Vaccine Institute
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Surgical Sciences
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Surgical Sciences Section for AIDS Research & Development
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203

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