905. Early Innate and Adaptive Immune Responses to Investigational Human Immunodeficiency Virus (HIV)-1 Vaccines (VRC 016 study)
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall

Background: A vaccine to prevent HIV remains a key goal in controlling the HIV epidemic. Evaluation of the recombinant six-plasmid DNA vaccine (DNA) and recombinant adenoviral serotype 5 vector vaccine (rAd5) began in 2004. These vaccines were assessed as immunogenic and safe but a Phase 2b study, HVTN 505, showed these vaccines were not effective in preventing HIV infection. This trial evaluated if the pattern of innate responses elicited by rAd5 vaccine after DNA priming is different from responses to rAd5 alone. Studying the pattern and kinetics of immune responses will help guide future HIV vaccine development.

Methods: Healthy adults, 18-50 years of age who were HIV vaccine na´ve, and adenovirus-5 seronegative were enrolled. The first 25 were randomized to receive either a single rAd5 vaccine (group1) or 3 doses of DNA vaccine at day 0, 28 and 56 followed by a rAd5 vaccine at day 168 (group2) and the last 11 subjects were enrolled into Group 2. Subjects were assessed for local and systemic reactogenicity. Following the rAd5 vaccine, both groups underwent interval blood sample collection 24hours after vaccination and over the next 28 days to measure cytokine levels.

Results: 36 subjects enrolled, 11 subjects in group 1 and 18 subjects in group 2 completed all vaccinations. No serious adverse events occurred. Local and systemic reactogenicity after study vaccinations was similar to prior studies typically mild and no more than moderate in severity. We compared plasma cytokine profiles using the MSD platform for groups 1 and 2. IL-4 (P=<0.0001), IL-5 (P=<0.0001), IL-12p70 (P=<0.0001) and IFN-γ (P=<0.0001) were all significantly different longitudinally, where the largest differences were noted around 18 hours for IFN-γ. This suggests a pattern of immune recall. Whereas, levels of IL-13 and TNF-α were higher in group 1 subjects but this was not significant.

Conclusion: Both rAd5 and recombinant DNA vaccines are safe, well tolerated and immunogenic. The pattern of immune responses is different in group 2 subjects who received a DNA prime and rAd5 boost vaccine regimen with a suggestion of recall immunity when compared to rAd5 alone.

Uzma Sarwar, MD1, Laura Novik, RN2, Mary Enama, M.A., PA-C2, Douglas Herrin, B.S.2, Sandeep Narpala, M.S.2, Adrian Mcdermott, M.Sc., PhD2, Barney S. Graham, MD, PhD, FIDSA3 and Julie Ledgerwood, D.O.2, (1)Infectious Diseases, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, (2)Vaccine Research Center, National Institutes of Health, Bethesda, MD, (3)National Institutes of Health/National Institute of Allergy and Infectious Diseases/Vaccine Research Center, Bethesda, MD

Disclosures:

U. Sarwar, None

L. Novik, None

M. Enama, None

D. Herrin, None

S. Narpala, None

A. Mcdermott, None

B. S. Graham, None

J. Ledgerwood, None

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