DNA Vaccine Delivered by a Needle-Free Injection Device Improves Potency of Priming for Antibody and CD8+ T-Cell Responses after rAd5 Boost in a Randomized Clinical Trial

Barney S Graham,Martha C Nason,The Vrc 008 Study Team ,Mary E Enama,Ingelise J Gordon,John R Mascola,Mario Roederer,Gary J Nabel,Richard A Koup,Sarah A Plummer,Robert T Bailer,Sheila A Peel,Julie E Ledgerwood

doi:10.1371/journal.pone.0059340

Abstract

BackgroundDNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector® device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity.MethodsForty adults, 18–50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector® 2000™ or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 1010 or 1011 particle units (PU). Equal numbers per assigned schedule had low (≤500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody.Results120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-γ ELISpot response rates were 17/19 (89%) for Biojector® and 13/17 (76%) for N/S delivery at Week 28 (4 weeks post rAd5 boost). The magnitude of ELISpot response was about 3-fold higher in Biojector® compared to N/S groups. Similar effects on response rates and magnitude were observed for CD8+, but not CD4+ T-cell responses by ICS. Env-specific antibody responses were about 10-fold higher in Biojector-primed subjects.ConclusionsDNA vaccination by Biojector® was well-tolerated and compared to needle injection, primed for greater IFN-γ ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.Trial RegistrationClinicalTrials.gov NCT00109629

Highlights

Immunization with plasmid DNA is a promising technology for gene-based antigen delivery
A variety of doses have been explored, and early in the program a decision was made to use the needle-free BiojectorH device based on published reports of BiojectorH delivery improving the antibody response to DNA vaccines in animals [11] and humans [12,13] compared to delivery by needle and syringe (N/ S)
Three doses of a West Nile virus (WNV) DNA vaccine expressing the prM and E proteins induced substantial neutralizing antibody responses comparable to those seen in horses known to be protected [6,8]

Summary

Introduction

Immunization with plasmid DNA is a promising technology for gene-based antigen delivery. A single dose of H5 influenza HA DNA vaccine primed a four-fold increase in HAI antibody titers in .80% of subjects following a single 6 month boost with unadjuvanted inactivated H5N1 vaccine compared to 2 doses of inactivated H5N1 vaccine [9] This concept is being evaluated in Phase II studies using seasonal influenza vaccines. In the HIV vaccine development program, DNA primed broad and durable T cell responses and consistent antibody responses following boosting with rAd5 [15,16,17,18] This regimen is being evaluated in the HVTN 505 Phase IIb test-of-concept study to determine efficacy. Needle-free delivery of DNA using a CO2-powered BiojectorH device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity

Objectives

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Results

Conclusion