Nanolipoprotein delivery enhances immunostimulatory properties of innate immune agonists and provides protection against lethal influenza challenge (P4218)

• Published in: The Journal of immunology (1950) Vol. 190; no. 1_Supplement; pp. 48 - 48.19
• Main Authors: Weilhammer, Dina, Alam, Shabnam, Blanchette, Craig, Fischer, Nicholas, Loots, Gabriela, Corzett, Michele, Thomas, Cindy, Hwang, Mona, Lychak, Cheri, Sant, Andrea, Rasley, Amy
• Format: Journal Article
• Language: English
• Published: 01.05.2013
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.48.19

Abstract Therapies targeting the innate immune system have the potential to provide transient, non-specific protection from a variety of infectious organisms. As such, we have employed a nanolipoprotein (NLP) platform to enhance the efficacy of synthetic innate immune agonists. NLPs are discoidal, nanometer-sized particles comprised of self-assembled phospholipid membranes and apolipoproteins. We demonstrate that the synthetic Toll-like receptor (TLR) ligands monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG ODNs) can be readily incorporated into NLPs. Further, conjugation of both MPLA and CpG ODNs to NLPs significantly enhances their immunostimulatory profiles in vivo compared to administration of agonists alone. Specifically, conjugation to NLPs promotes agonist trafficking to secondary lymphoid organs, enhances and prolongs stimulation of innate immune cells, significantly increases cytokine production, and enhances upregulation of myriad immunoregulatory genes in vivo. Importantly, enhancement of cytokine production by agonists conjugated to NLPs was also observed in primary human dendritic cells. Strikingly, BALB/c mice pretreated with NLP-CpG constructs prior to a lethal influenza challenge were protected from weight-loss induced death, whereas pretreatment with CpG alone had no effect on survival. Taken together, these data suggest that NLP:agonist conjugates potentially represent a novel therapeutic measure against emerging pathogens.