In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.
DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3095594?pdf=render |
| _version_ | 1819259510639820800 |
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| author | Sandhya Vasan Arlene Hurley Sarah J Schlesinger Drew Hannaman David F Gardiner Daniel P Dugin Mar Boente-Carrera Roselle Vittorino Marina Caskey Johanne Andersen Yaoxing Huang Josephine H Cox Tony Tarragona-Fiol Dilbinder K Gill Hannah Cheeseman Lorna Clark Len Dally Carol Smith Claudia Schmidt Harriet H Park Jakub T Kopycinski Jill Gilmour Patricia Fast Robert Bernard David D Ho |
| author_facet | Sandhya Vasan Arlene Hurley Sarah J Schlesinger Drew Hannaman David F Gardiner Daniel P Dugin Mar Boente-Carrera Roselle Vittorino Marina Caskey Johanne Andersen Yaoxing Huang Josephine H Cox Tony Tarragona-Fiol Dilbinder K Gill Hannah Cheeseman Lorna Clark Len Dally Carol Smith Claudia Schmidt Harriet H Park Jakub T Kopycinski Jill Gilmour Patricia Fast Robert Bernard David D Ho |
| author_sort | Sandhya Vasan |
| collection | DOAJ |
| description | DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987. |
| first_indexed | 2024-12-23T19:11:10Z |
| format | Article |
| id | doaj.art-54e6c0214ce848db98e3291e78e074a0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T19:11:10Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-54e6c0214ce848db98e3291e78e074a02022-12-21T17:34:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e1925210.1371/journal.pone.0019252In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.Sandhya VasanArlene HurleySarah J SchlesingerDrew HannamanDavid F GardinerDaniel P DuginMar Boente-CarreraRoselle VittorinoMarina CaskeyJohanne AndersenYaoxing HuangJosephine H CoxTony Tarragona-FiolDilbinder K GillHannah CheesemanLorna ClarkLen DallyCarol SmithClaudia SchmidtHarriet H ParkJakub T KopycinskiJill GilmourPatricia FastRobert BernardDavid D HoDNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987.http://europepmc.org/articles/PMC3095594?pdf=render |
| spellingShingle | Sandhya Vasan Arlene Hurley Sarah J Schlesinger Drew Hannaman David F Gardiner Daniel P Dugin Mar Boente-Carrera Roselle Vittorino Marina Caskey Johanne Andersen Yaoxing Huang Josephine H Cox Tony Tarragona-Fiol Dilbinder K Gill Hannah Cheeseman Lorna Clark Len Dally Carol Smith Claudia Schmidt Harriet H Park Jakub T Kopycinski Jill Gilmour Patricia Fast Robert Bernard David D Ho In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS ONE |
| title | In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. |
| title_full | In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. |
| title_fullStr | In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. |
| title_full_unstemmed | In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. |
| title_short | In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. |
| title_sort | in vivo electroporation enhances the immunogenicity of an hiv 1 dna vaccine candidate in healthy volunteers |
| url | http://europepmc.org/articles/PMC3095594?pdf=render |
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