Abstract
BackgroundDNA-based vaccines have been safe but weakly immunogenic in humans to date.Methods and FindingsWe 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.ConclusionsThis 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.Trial RegistrationClinicalTrials.gov NCT00545987
Highlights
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
In 1993, Ulmer et al first described the ability of naked plasmid DNA encoding an influenza protein to induce a protective immune response in mice [1], likely through transfection of myocytes and cross-presentation to antigen-presenting cells (APCs), as well as direct uptake of apoptotic cells by APCs [2]
DNA vaccines have been utilized in a variety of experimental clinical settings including candidate vaccines against cancer, malaria, hepatitis B, and HIV-1 [3,4,5,6,7]
Summary
In 1993, Ulmer et al first described the ability of naked plasmid DNA encoding an influenza protein to induce a protective immune response in mice [1], likely through transfection of myocytes and cross-presentation to antigen-presenting cells (APCs), as well as direct uptake of apoptotic cells by APCs [2]. The focus of many DNA vaccine strategies has shifted to their ability to ‘‘prime’’ the immune response before boosting with a recombinant live viral vector, such as adenovirus or modified vaccinia Ankara (MVA) [9,10,11,12], or with protein [13]. DNA vaccines offer several advantages over vaccines based on recombinant live viral vectors. DNA vaccines can be rapidly produced using relatively simple, low-cost manufacturing procedures and exhibit a favorable thermostability profile. Such features would confer obvious advantages in large-scale global vaccination campaigns. DNA-based vaccines have been safe but weakly immunogenic in humans to date
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
