Abstracts (complete list) - Wissenschaft Online

Edith Jasny, Martin Eisenblaetter, Tamara Visekruna, Klara Tenner-Racz, Christiane
Stahl-Hennig, Andres Salazar, Ralph M. Steinman, Klaus Ueberla, Mariagrazia
Uguccioni, Ralf Ignatius
Synthetic double-stranded RNA, Poly ICLC, enhances the
induction of cellular immune responses against protein
antigens in rhesus macaques
Background: Ligands for Toll-like receptors (TLRs) are promising adjuvants for the
induction of humoral and cellular immune responses, as in the design of AIDS vaccines.
Poly ICLC is a synthetic double-stranded RNA that should bind to TLR3 and has been
stabilized against serum nucleases, which are present in the plasma of primates.
Objectives: To study the effects of Poly ICLC on protein-specific immune responses of
rhesus macaques in vivo and assess its effects on leukocyte subsets in vitro.
Methods: Monkeys were immunized s.c. with keyhole limpet hemocyanin (KLH) together
with or without Poly ICLC. Draining lymph nodes were removed after 18 h, and cellular
and humoral immune responses were determined at several time points in standard
assays.
In vitro, human and monkey PBMCs or selected leukocyte subsets were incubated with
Poly ICLC +/- Lipofectamine and cellular activation and cytokine secretion were
monitored.
Results: The application of Poly ICLC led to elevated serum levels of CXCL9 and
CXCL10; both chemokines were also detected in draining lymph nodes by in situ
hybridization. KLH-specific cellular immune responses were stronger in Poly ICLC coinjected
animals than in controls and highest responses were observed in animals
injected with 0.5 mg/kg Poly ICLC. Humoral immune responses to KLH were enhanced
also by lower doses of Poly ICLC. The effect of Poly ICLC may not have been due to
direct activation of dendritic cells (DCs) because rhesus macaque monocyte-derived DCs
expressed little TLR3 as shown by flow cytometry. Likewise, we neither detected
increased numbers of mature DCs in the draining lymph nodes following Poly ICLC
injection nor could primary myeloid monkey DCs be activated by Poly ICLC in vitro.
Instead, Poly ICLC did activate NK cells in PBMCs, as indicated by CD69 upregulation. In
addition, Poly ICLC stimulated PBMCs secreted enhanced levels of CXCL9 and CXCL10.
Conclusion: Poly ICLC has activity as an adjuvant for the induction of protein-specific
cellular immune responses in monkeys.