Phase I randomized clinical trial of VRC DNA and rAd5 HIV-1 vaccine delivery by intramuscular (IM), subcutaneous (SC) and intradermal (ID) administration (VRC 011)

Mary E. Enama, Julie E. Ledgerwood, Laura Novik, Martha C. Nason, Ingelise J. Gordon, LaSonji Holman, Robert T. Bailer, Mario Roederer, Richard A. Koup, John R. Mascola, Gary J. Nabel, Barney S. Graham

Research output: Contribution to journalArticle

Abstract

Background: Phase 1 evaluation of the VRC HIV DNA and rAd5 vaccines delivered intramuscularly (IM) supported proceeding to a Phase 2 b efficacy study. Here we report comparison of the IM, subcutaneous (SC) and intradermal (ID) routes of administration. Methods: Sixty subjects were randomized to 6 schedules to evaluate the IM, SC or ID route for prime injections. Three schedules included DNA primes (Wks 0,4,8) and 3 schedules included rAd5 prime (Wk0); all included rAd5 IM boost (Wk24). DNA vaccine dosage was 4 mg IM or SC, but 0.4 mg ID, 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 ID and SC, but not IM 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 ID and SC injections differed from IM injections but all routes were well-tolerated. There was no evidence of an immunogenicity advantage following SC or ID delivery, supporting IM delivery as the preferred route of administration. Trial Registration: Clinicaltrials.gov NCT00321061.

Original languageEnglish (US)
Article numbere91366
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 12 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Enama, M. E., Ledgerwood, J. E., Novik, L., Nason, M. C., Gordon, I. J., Holman, L., Bailer, R. T., Roederer, M., Koup, R. A., Mascola, J. R., Nabel, G. J., & Graham, B. S. (2014). Phase I randomized clinical trial of VRC DNA and rAd5 HIV-1 vaccine delivery by intramuscular (IM), subcutaneous (SC) and intradermal (ID) administration (VRC 011). PLoS One, 9(3), [e91366]. https://doi.org/10.1371/journal.pone.0091366