Polyinosinic-Polycytidylic Acid-poly-L-lysine Carboxymethylcellulose (Poly-ICLC) in Healthy Volunteers
Status:
Completed
Trial end date:
2011-09-01
Target enrollment:
Participant gender:
Summary
Vaccines induce protective immunity against numerous infectious diseases. However, current
vaccines have limited efficacy against challenging infections like tuberculosis, malaria, and
HIV. Protein vaccines are safe but, typically they induce weak T cell immunity when
administered alone. Therefore, special attention is being given to adjuvants, which are
enhancers of immunity, that cab mature antigen presenting immunostimulatory dendritic cells.
Our goal is to study in humans the mechanism whereby a synthetic adjuvant, poly ICLC, which
acts on defined pattern recognition receptors, enhances T an B cell immunity. In preclinical
studies, our lab has found in mice that poly IC and its analog poly ICLC are superior
adjuvants for T cell mediated immunity relative to other agonists for PRR. Poly ICLC has been
extensively studied in humans with a favorable safety profile. In a recently completed Phase
I study, poly ICLC was found to be safe and well tolerated when administered as a single dose
of 1.6 mg subcutaneously and intranasally to healthy volunteers. In additional, preliminary
data shows marked upregulation of gene expression in whole PBMSc following s.c. injection of
poly ICLC as well as activation of various blood cell type, including dendritic cells and
monocytes. In this study the investigators propose to extend the evaluation of innate immune
responses following s.d. injection of poly ICLC to healthy volunteers. The investigators
propose to characterize poly ICLC effects on specific blood cell types, focusing on three
different subsets of DC's, by analyzing gene transcriptional changes at baseline and at one
day following its administration. In order to study the early local effects of poly ICLC,
which are important for the recruitment and activation of antigen presenting cells, the
investigators also propose to perform skin biopsies at a skin site contralateral to the
injection site and at the injection site after poly ICLC injections.