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
Year of Publication
Graham, BS; Enama, ME; Nason, MC; Gordon, IJ; Peel, SA; Ledgerwood, JE; Plummer, SA; Mascola, JR; Bailer, RT; Roederer, M; Koup, RA; Nabel, GJ; The VRC 008 Study Team
Adenoviridae/genetics; Antibodies; CD8-Positive T-Lymphocytes/immunology; Cellular/immunology; DNA; Dose-Response Relationship; HIV-1/immunology/metabolism; Humoral/immunology; Immunity; Immunologic; Recombinant/genetics; Viral/immunology
BACKGROUND: DNA vaccine immunogenicity has been limited by inefficient delivery. Needle-free delivery of DNA using a CO2-powered Biojector(R) device was compared to delivery by needle and syringe and evaluated for safety and immunogenicity. METHODS: Forty adults, 18-50 years, were randomly assigned to intramuscular (IM) vaccinations with DNA vaccine, VRC-HIVDNA016-00-VP, (weeks 0, 4, 8) by Biojector(R) 2000 or needle and syringe (N/S) and boosted IM at week 24 with VRC-HIVADV014-00-VP (rAd5) with N/S at 10(10) or 10(11) particle units (PU). Equal numbers per assigned schedule had low (=500) or high (>500) reciprocal titers of preexisting Ad5 neutralizing antibody. RESULTS: 120 DNA and 39 rAd5 injections were given; 36 subjects completed follow-up research sample collections. IFN-gamma ELISpot response rates were 17/19 (89%) for Biojector(R) 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(R) 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. CONCLUSIONS: DNA vaccination by Biojector(R) was well-tolerated and compared to needle injection, primed for greater IFN-gamma ELISpot, CD8+ T-cell, and antibody responses after rAd5 boosting.