Dendritic cell maturation and activation via RNA/DNA danger signals : co-delivery of protein antigen with siRNA or CpG DNA

Traditional vaccines consisting of live attenuated pathogens or inactivated toxins cannot be readily applied to the more challenging diseases of the present e.g. hepatitis C and the human immunodeficiency virus. As such, there is a need to develop new methods of priming the immune system against such foreign invaders. Recombinant protein subunits and peptides are relatively safe alternatives to live attenuated pathogens. However, these antigens are poorly immunogenic when administered alone in solution form and thus require the use of an adjuvant. To this end, we have developed a hydrogel-based nanoparticulate system to encapsulate protein antigen and to co-deliver it with DNA/RNA-based adjuvants to dendritic cells, the key antigen presenting cells in primary immune responses. Using CpG oligonucleotides or siRNA as adjuvants, we observed via enzyme-linked immunosorbent assays for interleukin 12 and interferon-[alpha], respectively, that DCs were activated by CpG oligonucleotide- and siRNA-functionalized nanoparticles [approx.]10-fold more potently than by soluble CpG or siRNA ligands.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Yap, Jonathan Woon Teck

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38449

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38449