VRC 011 Baseline Characteristics of Participants.

<p>VRC 011 Baseline Characteristics of Participants.</p

Maximum Systemic Reactogenicity Summary for All Vaccinations.

<p>Maximum Systemic Reactogenicity Summary for All Vaccinations.</p

ELISA responses among the different groups after priming by route and vaccine indicated on X-axis (A) and boosting with rAd5 IM (B).

<p>The numbers above each boxplot represent the fraction of participants in each group with available data at that time point who were judged to be responders using predefined criteria. The responders are represented on the plot with red dots, and are used to construct the boxplots; blue points represent non-responders and are not included in the boxplots.</p

Listing of Unsolicited Local Reactions After Prime Injections.

<p>Listing of Unsolicited Local Reactions After Prime Injections.</p

ELISpot responses among the different groups after priming with vaccine and route indicated on X-axis (panel A) and after rAd5 boosting IM (panel B).

<p>The numbers above each boxplot represent the fraction of participants in each group with available data at that time point who were judged to be responders using predefined criteria. The responders are represented on the plot with red dots, and are used to construct the boxplots; blue points represent non-responders and are not included in the boxplots.</p

Frequency of Vaccine-Induced Seropositivity/Reactivity Through Study Week 42.

<p>Subjects were tested at weeks 12, 30 and 42 regardless of the number of vaccines completed. This shows frequency of a “reactive EIA” using a commercial diagnostic kit (Abbott HIV-1/HIV-2 rDNA) at any time during the study. Western blot was performed only for samples with positive EIA. HIV uninfected status was confirmed by RNA PCR tests, which were consistently negative for all subjects throughout the study.</p

VRC 011 Disposition Flow Diagram of Screening, Randomization and Vaccination Completion.

<p>VRC 011 Disposition Flow Diagram of Screening, Randomization and Vaccination Completion.</p

ICS responses among the different priming groups after boosting with rAd5 IM for CD4 T cells (A) and CD8 T cells (B).

<p>The numbers above each boxplot represent the fraction of participants in each group with available data at that time point who were judged to be responders using predefined positivitycriteria. The responders are represented on the plot with red dots, and are used to construct the boxplots; blue points represent non-responders and are not included in the boxplots.</p

Maximum Local Reactogenicity Summary for All Vaccinations.

<p>Maximum Local Reactogenicity Summary for All Vaccinations.</p

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)

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial Registration</p><p><a href="http://tinyurl.com/muzmnub" target="_blank">Clinicaltrials.gov NCT00321061</a></p></div