Loading…
Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity
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). Low-risk, healthy adult subjects were enrolled i...
Saved in:
Published in: | PloS one 2010-08, Vol.5 (8), p.e11995 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3 |
---|---|
cites | cdi_FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3 |
container_end_page | |
container_issue | 8 |
container_start_page | e11995 |
container_title | PloS one |
container_volume | 5 |
creator | Graham, Barney S McElrath, M Juliana Keefer, Michael C Rybczyk, Kyle Berger, David Weinhold, Kent J Ottinger, Janet Ferarri, Guido Montefiori, David C Stablein, Don Smith, Carol Ginsberg, Richard Eldridge, John Duerr, Ann Fast, Pat Haynes, Barton F |
description | 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).
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.
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.
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.
ClinicalTrials.gov NCT00000886. |
doi_str_mv | 10.1371/journal.pone.0011995 |
format | article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1292249564</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A473878459</galeid><doaj_id>oai_doaj_org_article_7b1d67d0fd75491fa58e960e942cbeb3</doaj_id><sourcerecordid>A473878459</sourcerecordid><originalsourceid>FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3</originalsourceid><addsrcrecordid>eNqNk11rFDEUhgdRbK3-A9GAoAjumo9JZnIjlKJ2oVCw2ttwJsnsps4k20mmWv-Gf9iMuy1d6YXMRWZOnvfN5HwUxXOC54RV5P1FGAcP3XwdvJ1jTIiU_EGxTySjM0Exe3jnfa94EuMFxpzVQjwu9iiusBCM7he_F30_evcLkgse_XBphXTQ3xO4DoUWHS_OZ8YO7soatLbr5IyNyHnUB5_A5y-0ODuccYJcDk9OYWm90-9QMyakYYwZjykbdBZBE7WNUwS8QaMHrbMjNHlrsKDTRurS9dPiUQtdtM-260Hx7dPHr0fHs5PTz4ujw5OZrihLM1k2hgnDjMDM1k3bttyIkgEFyqm1gkpGRCUAqhpT4KZtZGtqrhtWCsBlww6KlxvfdRei2uYzKkIlpaXk2eugWGwIE-BCrQfXw3CtAjj1NxCGpYIhOd1ZVTXEiMrg1lS8lKQFXlspsJUl1Y1tWPb6sD1tbHprtPVpgG7HdHfHu5VahitFZa5jTbPBm63BEC5HG5PqXc5o14G3YYyq4jw3BiUT-eof8v7Lbakl5P93vg35WD15qsOyYnVVl1xman4PlR9je6dz77W5truCtzuCzCT7My1zM0S1OPvy_-zp-S77-g67stClVQzdODVu3AXLDaiHEONg29scE6ym0bnJhppGR21HJ8te3K3PrehmVtgfTjQWWg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1292249564</pqid></control><display><type>article</type><title>Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Graham, Barney S ; McElrath, M Juliana ; Keefer, Michael C ; Rybczyk, Kyle ; Berger, David ; Weinhold, Kent J ; Ottinger, Janet ; Ferarri, Guido ; Montefiori, David C ; Stablein, Don ; Smith, Carol ; Ginsberg, Richard ; Eldridge, John ; Duerr, Ann ; Fast, Pat ; Haynes, Barton F</creator><contributor>Ndhlovu, Lishomwa C.</contributor><creatorcontrib>Graham, Barney S ; McElrath, M Juliana ; Keefer, Michael C ; Rybczyk, Kyle ; Berger, David ; Weinhold, Kent J ; Ottinger, Janet ; Ferarri, Guido ; Montefiori, David C ; Stablein, Don ; Smith, Carol ; Ginsberg, Richard ; Eldridge, John ; Duerr, Ann ; Fast, Pat ; Haynes, Barton F ; AIDS Vaccine Evaluation Group ; the AIDS Vaccine Evaluation Group ; Ndhlovu, Lishomwa C.</creatorcontrib><description>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).
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.
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.
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.
ClinicalTrials.gov NCT00000886.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0011995</identifier><identifier>PMID: 20706632</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abscess ; Abscess - etiology ; Abscesses ; Acquired immune deficiency syndrome ; Adaptive immunity ; Adjuvants ; Adolescent ; Adult ; AIDS ; AIDS vaccines ; Antibody Formation - immunology ; Antigen-antibody reactions ; Antigenic determinants ; Antigens ; Assaying ; B7 antigen ; CD4 antigen ; CD8 antigen ; Chills ; Chromium radioisotopes ; Cryopreservation ; Cytotoxicity ; Development and progression ; Enzyme-linked immunosorbent assay ; Epitopes ; Female ; Freund's Adjuvant - immunology ; Freund's incomplete adjuvant ; Headache ; Highly active antiretroviral therapy ; Histocompatibility antigen HLA ; HIV ; HIV-1 ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Immune response ; Immunization ; Immunization - adverse effects ; Immunization - methods ; Immunogenicity ; Immunology/Immune Response ; Immunology/Immunity to Infections ; Immunology/Innate Immunity ; Infectious Diseases/HIV Infection and AIDS ; Infectious Diseases/Viral Infections ; Lymphocytes B ; Lymphocytes T ; Male ; Manganese ; Mannitol - analogs & derivatives ; Microbiology/Immunity to Infections ; Microbiology/Innate Immunity ; Middle Aged ; Myalgia ; Nausea ; Neutralization ; Oleic Acids ; Pain ; Peptides ; Peptides - adverse effects ; Peptides - immunology ; Public Health and Epidemiology/Global Health ; Public Health and Epidemiology/Immunization ; Public Health and Epidemiology/Infectious Diseases ; Public Health and Epidemiology/Preventive Medicine ; Risk reduction ; T cells ; T-Lymphocytes - immunology ; Vaccines ; Vaccines, Subunit - adverse effects ; Vaccines, Subunit - immunology ; Virology/Host Antiviral Responses ; Virology/Immunodeficiency Viruses ; Virology/Vaccines ; Young Adult</subject><ispartof>PloS one, 2010-08, Vol.5 (8), p.e11995</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3</citedby><cites>FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1292249564/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1292249564?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20706632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ndhlovu, Lishomwa C.</contributor><creatorcontrib>Graham, Barney S</creatorcontrib><creatorcontrib>McElrath, M Juliana</creatorcontrib><creatorcontrib>Keefer, Michael C</creatorcontrib><creatorcontrib>Rybczyk, Kyle</creatorcontrib><creatorcontrib>Berger, David</creatorcontrib><creatorcontrib>Weinhold, Kent J</creatorcontrib><creatorcontrib>Ottinger, Janet</creatorcontrib><creatorcontrib>Ferarri, Guido</creatorcontrib><creatorcontrib>Montefiori, David C</creatorcontrib><creatorcontrib>Stablein, Don</creatorcontrib><creatorcontrib>Smith, Carol</creatorcontrib><creatorcontrib>Ginsberg, Richard</creatorcontrib><creatorcontrib>Eldridge, John</creatorcontrib><creatorcontrib>Duerr, Ann</creatorcontrib><creatorcontrib>Fast, Pat</creatorcontrib><creatorcontrib>Haynes, Barton F</creatorcontrib><creatorcontrib>AIDS Vaccine Evaluation Group</creatorcontrib><creatorcontrib>the AIDS Vaccine Evaluation Group</creatorcontrib><title>Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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).
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.
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.
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.
ClinicalTrials.gov NCT00000886.</description><subject>Abscess</subject><subject>Abscess - etiology</subject><subject>Abscesses</subject><subject>Acquired immune deficiency syndrome</subject><subject>Adaptive immunity</subject><subject>Adjuvants</subject><subject>Adolescent</subject><subject>Adult</subject><subject>AIDS</subject><subject>AIDS vaccines</subject><subject>Antibody Formation - immunology</subject><subject>Antigen-antibody reactions</subject><subject>Antigenic determinants</subject><subject>Antigens</subject><subject>Assaying</subject><subject>B7 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Chills</subject><subject>Chromium radioisotopes</subject><subject>Cryopreservation</subject><subject>Cytotoxicity</subject><subject>Development and progression</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epitopes</subject><subject>Female</subject><subject>Freund's Adjuvant - immunology</subject><subject>Freund's incomplete adjuvant</subject><subject>Headache</subject><subject>Highly active antiretroviral therapy</subject><subject>Histocompatibility antigen HLA</subject><subject>HIV</subject><subject>HIV-1</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunization</subject><subject>Immunization - adverse effects</subject><subject>Immunization - methods</subject><subject>Immunogenicity</subject><subject>Immunology/Immune Response</subject><subject>Immunology/Immunity to Infections</subject><subject>Immunology/Innate Immunity</subject><subject>Infectious Diseases/HIV Infection and AIDS</subject><subject>Infectious Diseases/Viral Infections</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Manganese</subject><subject>Mannitol - analogs & derivatives</subject><subject>Microbiology/Immunity to Infections</subject><subject>Microbiology/Innate Immunity</subject><subject>Middle Aged</subject><subject>Myalgia</subject><subject>Nausea</subject><subject>Neutralization</subject><subject>Oleic Acids</subject><subject>Pain</subject><subject>Peptides</subject><subject>Peptides - adverse effects</subject><subject>Peptides - immunology</subject><subject>Public Health and Epidemiology/Global Health</subject><subject>Public Health and Epidemiology/Immunization</subject><subject>Public Health and Epidemiology/Infectious Diseases</subject><subject>Public Health and Epidemiology/Preventive Medicine</subject><subject>Risk reduction</subject><subject>T cells</subject><subject>T-Lymphocytes - immunology</subject><subject>Vaccines</subject><subject>Vaccines, Subunit - adverse effects</subject><subject>Vaccines, Subunit - immunology</subject><subject>Virology/Host Antiviral Responses</subject><subject>Virology/Immunodeficiency Viruses</subject><subject>Virology/Vaccines</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11rFDEUhgdRbK3-A9GAoAjumo9JZnIjlKJ2oVCw2ttwJsnsps4k20mmWv-Gf9iMuy1d6YXMRWZOnvfN5HwUxXOC54RV5P1FGAcP3XwdvJ1jTIiU_EGxTySjM0Exe3jnfa94EuMFxpzVQjwu9iiusBCM7he_F30_evcLkgse_XBphXTQ3xO4DoUWHS_OZ8YO7soatLbr5IyNyHnUB5_A5y-0ODuccYJcDk9OYWm90-9QMyakYYwZjykbdBZBE7WNUwS8QaMHrbMjNHlrsKDTRurS9dPiUQtdtM-260Hx7dPHr0fHs5PTz4ujw5OZrihLM1k2hgnDjMDM1k3bttyIkgEFyqm1gkpGRCUAqhpT4KZtZGtqrhtWCsBlww6KlxvfdRei2uYzKkIlpaXk2eugWGwIE-BCrQfXw3CtAjj1NxCGpYIhOd1ZVTXEiMrg1lS8lKQFXlspsJUl1Y1tWPb6sD1tbHprtPVpgG7HdHfHu5VahitFZa5jTbPBm63BEC5HG5PqXc5o14G3YYyq4jw3BiUT-eof8v7Lbakl5P93vg35WD15qsOyYnVVl1xman4PlR9je6dz77W5truCtzuCzCT7My1zM0S1OPvy_-zp-S77-g67stClVQzdODVu3AXLDaiHEONg29scE6ym0bnJhppGR21HJ8te3K3PrehmVtgfTjQWWg</recordid><startdate>20100810</startdate><enddate>20100810</enddate><creator>Graham, Barney S</creator><creator>McElrath, M Juliana</creator><creator>Keefer, Michael C</creator><creator>Rybczyk, Kyle</creator><creator>Berger, David</creator><creator>Weinhold, Kent J</creator><creator>Ottinger, Janet</creator><creator>Ferarri, Guido</creator><creator>Montefiori, David C</creator><creator>Stablein, Don</creator><creator>Smith, Carol</creator><creator>Ginsberg, Richard</creator><creator>Eldridge, John</creator><creator>Duerr, Ann</creator><creator>Fast, Pat</creator><creator>Haynes, Barton F</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100810</creationdate><title>Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity</title><author>Graham, Barney S ; McElrath, M Juliana ; Keefer, Michael C ; Rybczyk, Kyle ; Berger, David ; Weinhold, Kent J ; Ottinger, Janet ; Ferarri, Guido ; Montefiori, David C ; Stablein, Don ; Smith, Carol ; Ginsberg, Richard ; Eldridge, John ; Duerr, Ann ; Fast, Pat ; Haynes, Barton F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Abscess</topic><topic>Abscess - etiology</topic><topic>Abscesses</topic><topic>Acquired immune deficiency syndrome</topic><topic>Adaptive immunity</topic><topic>Adjuvants</topic><topic>Adolescent</topic><topic>Adult</topic><topic>AIDS</topic><topic>AIDS vaccines</topic><topic>Antibody Formation - immunology</topic><topic>Antigen-antibody reactions</topic><topic>Antigenic determinants</topic><topic>Antigens</topic><topic>Assaying</topic><topic>B7 antigen</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Chills</topic><topic>Chromium radioisotopes</topic><topic>Cryopreservation</topic><topic>Cytotoxicity</topic><topic>Development and progression</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epitopes</topic><topic>Female</topic><topic>Freund's Adjuvant - immunology</topic><topic>Freund's incomplete adjuvant</topic><topic>Headache</topic><topic>Highly active antiretroviral therapy</topic><topic>Histocompatibility antigen HLA</topic><topic>HIV</topic><topic>HIV-1</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunization</topic><topic>Immunization - adverse effects</topic><topic>Immunization - methods</topic><topic>Immunogenicity</topic><topic>Immunology/Immune Response</topic><topic>Immunology/Immunity to Infections</topic><topic>Immunology/Innate Immunity</topic><topic>Infectious Diseases/HIV Infection and AIDS</topic><topic>Infectious Diseases/Viral Infections</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Manganese</topic><topic>Mannitol - analogs & derivatives</topic><topic>Microbiology/Immunity to Infections</topic><topic>Microbiology/Innate Immunity</topic><topic>Middle Aged</topic><topic>Myalgia</topic><topic>Nausea</topic><topic>Neutralization</topic><topic>Oleic Acids</topic><topic>Pain</topic><topic>Peptides</topic><topic>Peptides - adverse effects</topic><topic>Peptides - immunology</topic><topic>Public Health and Epidemiology/Global Health</topic><topic>Public Health and Epidemiology/Immunization</topic><topic>Public Health and Epidemiology/Infectious Diseases</topic><topic>Public Health and Epidemiology/Preventive Medicine</topic><topic>Risk reduction</topic><topic>T cells</topic><topic>T-Lymphocytes - immunology</topic><topic>Vaccines</topic><topic>Vaccines, Subunit - adverse effects</topic><topic>Vaccines, Subunit - immunology</topic><topic>Virology/Host Antiviral Responses</topic><topic>Virology/Immunodeficiency Viruses</topic><topic>Virology/Vaccines</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graham, Barney S</creatorcontrib><creatorcontrib>McElrath, M Juliana</creatorcontrib><creatorcontrib>Keefer, Michael C</creatorcontrib><creatorcontrib>Rybczyk, Kyle</creatorcontrib><creatorcontrib>Berger, David</creatorcontrib><creatorcontrib>Weinhold, Kent J</creatorcontrib><creatorcontrib>Ottinger, Janet</creatorcontrib><creatorcontrib>Ferarri, Guido</creatorcontrib><creatorcontrib>Montefiori, David C</creatorcontrib><creatorcontrib>Stablein, Don</creatorcontrib><creatorcontrib>Smith, Carol</creatorcontrib><creatorcontrib>Ginsberg, Richard</creatorcontrib><creatorcontrib>Eldridge, John</creatorcontrib><creatorcontrib>Duerr, Ann</creatorcontrib><creatorcontrib>Fast, Pat</creatorcontrib><creatorcontrib>Haynes, Barton F</creatorcontrib><creatorcontrib>AIDS Vaccine Evaluation Group</creatorcontrib><creatorcontrib>the AIDS Vaccine Evaluation Group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Science in Context</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graham, Barney S</au><au>McElrath, M Juliana</au><au>Keefer, Michael C</au><au>Rybczyk, Kyle</au><au>Berger, David</au><au>Weinhold, Kent J</au><au>Ottinger, Janet</au><au>Ferarri, Guido</au><au>Montefiori, David C</au><au>Stablein, Don</au><au>Smith, Carol</au><au>Ginsberg, Richard</au><au>Eldridge, John</au><au>Duerr, Ann</au><au>Fast, Pat</au><au>Haynes, Barton F</au><au>Ndhlovu, Lishomwa C.</au><aucorp>AIDS Vaccine Evaluation Group</aucorp><aucorp>the AIDS Vaccine Evaluation Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-08-10</date><risdate>2010</risdate><volume>5</volume><issue>8</issue><spage>e11995</spage><pages>e11995-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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).
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.
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.
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.
ClinicalTrials.gov NCT00000886.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20706632</pmid><doi>10.1371/journal.pone.0011995</doi><tpages>e11995</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2010-08, Vol.5 (8), p.e11995 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1292249564 |
source | Publicly Available Content Database; PubMed Central |
subjects | Abscess Abscess - etiology Abscesses Acquired immune deficiency syndrome Adaptive immunity Adjuvants Adolescent Adult AIDS AIDS vaccines Antibody Formation - immunology Antigen-antibody reactions Antigenic determinants Antigens Assaying B7 antigen CD4 antigen CD8 antigen Chills Chromium radioisotopes Cryopreservation Cytotoxicity Development and progression Enzyme-linked immunosorbent assay Epitopes Female Freund's Adjuvant - immunology Freund's incomplete adjuvant Headache Highly active antiretroviral therapy Histocompatibility antigen HLA HIV HIV-1 Human immunodeficiency virus Human immunodeficiency virus 1 Humans Immune response Immunization Immunization - adverse effects Immunization - methods Immunogenicity Immunology/Immune Response Immunology/Immunity to Infections Immunology/Innate Immunity Infectious Diseases/HIV Infection and AIDS Infectious Diseases/Viral Infections Lymphocytes B Lymphocytes T Male Manganese Mannitol - analogs & derivatives Microbiology/Immunity to Infections Microbiology/Innate Immunity Middle Aged Myalgia Nausea Neutralization Oleic Acids Pain Peptides Peptides - adverse effects Peptides - immunology Public Health and Epidemiology/Global Health Public Health and Epidemiology/Immunization Public Health and Epidemiology/Infectious Diseases Public Health and Epidemiology/Preventive Medicine Risk reduction T cells T-Lymphocytes - immunology Vaccines Vaccines, Subunit - adverse effects Vaccines, Subunit - immunology Virology/Host Antiviral Responses Virology/Immunodeficiency Viruses Virology/Vaccines Young Adult |
title | Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T06%3A36%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Immunization%20with%20cocktail%20of%20HIV-derived%20peptides%20in%20montanide%20ISA-51%20is%20immunogenic,%20but%20causes%20sterile%20abscesses%20and%20unacceptable%20reactogenicity&rft.jtitle=PloS%20one&rft.au=Graham,%20Barney%20S&rft.aucorp=AIDS%20Vaccine%20Evaluation%20Group&rft.date=2010-08-10&rft.volume=5&rft.issue=8&rft.spage=e11995&rft.pages=e11995-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0011995&rft_dat=%3Cgale_plos_%3EA473878459%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c723t-94bd36d3d603e8bfff5d643a2a252ee62931676aa7802a5dfb9fd85cb346a04b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1292249564&rft_id=info:pmid/20706632&rft_galeid=A473878459&rfr_iscdi=true |