Faculty Collaboration Database

TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis. J Immunol 2010 Sep 01;185(5):2989-97

Date

07/28/2010

Pubmed ID

20660705

Pubmed Central ID

PMC3753007

DOI

10.4049/jimmunol.1000768

Scopus ID

2-s2.0-78049361384 (requires institutional sign-in at Scopus site)   100 Citations

Abstract

Vaccines that activate humoral and cell-mediated immune responses are urgently needed for many infectious agents, including the flaviviruses dengue and West Nile (WN) virus. Vaccine development would be greatly facilitated by a new approach, in which nanoscale modules (Ag, adjuvant, and carrier) are assembled into units that are optimized for stimulating immune responses to a specific pathogen. Toward that goal, we formulated biodegradable nanoparticles loaded with Ag and surface modified with the pathogen-associated molecular pattern CpG oligodeoxynucleotides. We chose to evaluate our construct using a recombinant envelope protein Ag from the WN virus and tested the efficiency of this system in eliciting humoral and cellular responses and providing protection against the live virus. Animals immunized with this system showed robust humoral responses polarized toward Th1 immune responses compared with predominately Th2-biased responses with the adjuvant aluminum hydroxide. Immunization with CpG oligodeoxynucleotide-modified nanoparticles resulted in a greater number of circulating effector T cells and greater activity of Ag-specific lymphocytes than unmodified nanoparticles or aluminum hydroxide. Ultimately, compared with alum, this system offered superior protection in a mouse model of WN virus encephalitis.

Author List

Demento SL, Bonafé N, Cui W, Kaech SM, Caplan MJ, Fikrig E, Ledizet M, Fahmy TM

MESH terms used to index this publication - Major topics in bold

Animals
Avidin
Biocompatible Materials
Biotin
Cells, Cultured
Drosophila
Gene Targeting
Genetic Vectors
Mice
Nanoparticles
Oligodeoxyribonucleotides
Th1 Cells
Th2 Cells
Toll-Like Receptor 9
West Nile Fever
West Nile Virus Vaccines
West Nile virus