The mechanisms that underlie the potent Th1-adjuvant capacity of poly(methyl vinyl ether-co-maleic anhydride)
nanoparticles (NPs) were investigated. Traditionally, polymer NPs have been considered delivery
systems that promote a closer interaction between antigen and antigen-presenting cells (APCs). Our results
revealed that poly(anhydride) NPs also act as agonists of various Toll-like receptors (TLRs) (TLR2, -4, and -5),
triggering a Th1-profile cytokine release (gamma interferon [IFN- ], 478 pg/ml versus 39.6 pg/ml from
negative control; interleukin-12 [IL-12], 40 pg/ml versus 7.2 pg/ml from negative control) and, after incubation
with dendritic cells, inducing a 2.5- to 3.5-fold increase of CD54 and CD86 costimulatory molecule expression.
Furthermore, in vivo studies suggest that NPs actively elicit a CD8 T-cell response. Immunization with empty
NPs resulted in a significant delay in the mean survival date (from day 7 until day 23 postchallenge) and a
protection level of 30% after challenge against a lethal dose of Salmonella enterica serovar Enteritidis. Taken
together, our results provide a better understanding of how NPs act as active Th1 adjuvants in immunoprophylaxis
and immunotherapy through TLR exploitation
