RT Journal Article
SR Electronic
T1 Rapid and systemic innate immune responses to an adenoviral HIV vaccine (45.27)
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 45.27
OP 45.27
VO 182
IS 1 Supplement
A1 Andersen-Nissen, Erica
A1 Zak, Daniel E
A1 Duerr, Ann C
A1 Peterson, Eric R
A1 Robertson, Michael N
A1 DeRosa, Stephen C
A1 McElrath, M. Juliana
A1 (HVTN), and the NIAID-sponsored HIV Vaccine Trials Network
YR 2009
UL http://www.jimmunol.org/content/182/1_Supplement/45.27.abstract
AB Understanding innate immune responses to candidate HIV vaccines will guide vaccine design. We assessed the early innate response in volunteers enrolled in HVTN 071, a trial of intramuscularly delivered Merck adenovirus serotype 5 (MRKAd5) gag/pol/nef- the same vaccine used in the Step trial. Samples were collected pre-vaccination and at 4-6 hours, days 1, 3, and 7 (n=11) post-vaccination or at day 1 post-vaccination (n=24). Cytokine and chemokine levels in the serum were measured by multiplex assay and cell populations were analyzed by multiparameter flow cytometry. Serum levels of IP-10, MCP-1, TNF-α, IL-6, IL-1RA, IFN-γ, and IL-10 were similar at baseline and 4-6 hours post-vaccination, showed up to 10-fold increases over baseline on day 1 post-vaccination, and returned to baseline levels by day 3. Dendritic cell concentrations increased in 4 hours; monocytes increased gradually and peaked at day 3. In contrast, T, B, and NK cell blood concentrations decreased sharply at day 1 post-vaccination, suggesting massive trafficking to the vaccination site. Moreover, PBMC gene expression analysis by microarray consistently revealed strong induction of inflammatory and antiviral genes. Together, these data demonstrate robust early immune activation after vaccination. Future studies of innate immune responses to other candidate HIV vaccines may elucidate why the vaccine used in the Step trial did not show efficacy.