Polyinosinic-Polycytidylic Acid-poly-L-lysine Carboxymethylcellulose (Poly-ICLC) in Healthy Volunteers
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||An Open Label Study to Evaluate Innate Immune Responses Induced by a Pattern Recognition Receptor Agonist, Poly-ICLC (Hiltonol), in Healthy Volunteers|
- To evaluate the innate immune responses to poly ICLC in different blood cell types, including three subsets of dendritic cells after subcutaneous administration to healthy volunteers. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
The variables to be assessed include:
- Transcriptional arrays in whole PBMCs and in 8 subsets of blood leukocytes (naïve and memory T, NK, B, monocytes and three different subsets of dendritic cells (BDCA1+, BDCA3+ and BDCA2+ plasmacytoid DCs) following s.c. administration of poly ICLC.
- Flow cytometric analysis of activation markers in different subsets of blood leukocytes.
- Measurement of cytokines in the serum and/or plasma following s.c. administration of poly ICLC.
- To evaluate the reproducibility of innate immune responses in whole PBMCs after a second dose of poly ICLC, in volunteers who participated in protocol MAC-682 and now return to participate in this proposed study. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
The following variable will be assessed:
- Transcriptional analysis of whole PBMC samples at different timepoints following the first dose and the second dose of poly ICLC in volunteers who participated in protocol MAC-682 and are now returning to participate in this proposed study.
- To evaluate innate immune responses to poly ICLC at the injection site. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
The following will be assessed:
- Routine histology and immunohistochemistry to evaluate cellular infiltrates following subcutaneous injection of poly ICLC.
- Transcriptional analysis of skin samples from study drug injection site and from a non-lesional site of skin.
|Study Start Date:||June 2011|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
Experimental: Poly ICLC
One 1.6 mg subcutaneous injection of the adjuvant, poly ICLC, in the upper arm.
Drug: Poly ICLC
One 1.6 mg subcutaneous injection of the study drug, poly ICLC in the upper arm.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01299662
|United States, New York|
|The Rockefeller University|
|New York, New York, United States, 10065|
|Principal Investigator:||Marina Caskey, MD||The Rockefeller University|