Phase I Randomized Clinical Trial of VRC DNA and rAd5 HIV-1 Vaccine Delivery by Intramuscular (i.m.), Subcutaneous (s.c.) and Intradermal (i.d.) Administration (VRC 011)
Year of Publication
Enama, ME; Ledgerwood, JE; Novik, L; Nason, MC; Gordon, IJ; Holman, L; Bailer, RT; Roederer, M; Koup, RA; Mascola, JR; Nabel, GJ; Graham, BS; The VRC 011 Study Team
Adenoviridae; AIDS Vaccines; Antibodies; DNA; DNA Recombinant; Injections; safety; T-Lymphocytes/immunology; Vaccines; Viral/immunology
BACKGROUND: Phase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (i.m.) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the i.m., subcutaneous (s.c.) and intradermal (i.d.) routes of administration. METHODS: Sixty subjects were randomized to 6 schedules to evaluate the i.m., s.c. or i.d. route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 i.m. boost (Wk24). DNA vaccine dosage was 4 mg i.m. or s.c., but 0.4 mg i.d., while all rAd5 vaccinations were 1010 PU. All injections were administered by needle and syringe. RESULTS: Overall, 27/30 subjects completed 3 DNA primes; 30/30 subjects completed rAd5 primes. Mild local pruritus (itchiness), superficial skin lesions and injection site nodules were associated with i.d. and s.c., but not i.m. injections. All routes induced T-cell and antibody immune responses after rAd5 boosting. Overall, >95% had Env antibody and >80% had Env T-cell responses. CONCLUSIONS: The pattern of local reactogenicity following i.d. and s.c. injections differed from i.m. injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following s.c. or i.d. delivery, supporting i.m. delivery as the preferred route of administration.