Immunostimulatory compositions and methods of use thereof

摘要

Lipid conjugates for enhanced delivery of cargo to the lymph nodes are disclosed. The lipid conjugates typically include three domains: a lipophilic domain that binds to albumin, a polar block domain, and a cargo such as a molecular adjuvant or immunostimulatory compound (such as an oligonucleotide) or antigenic peptide. Depending on the cargo, the length and compositions of the polar block can be tailored to push the equilibrium toward albumin binding, stable micelle formation, or cell insertion. The conjugates can be administered to a subject, for example, a subject with cancer or an infection, to induce or enhance a robust immune response in the subject.

主权项

1. A vaccine adjuvant comprising a plurality of amphiphilic albumin-binding conjugates, wherein the conjugate comprises
(a) a lipid component; (b) an optional polar component; and (c) an immunomodulatory compound or molecular adjuvant; wherein the immunomodulatory compound or molecular adjuvant is covalently linked to the lipid via a nucleotide or oligonucleotide linker comprising “n” guanines, wherein n is 1-10, wherein the conjugate is sufficiently soluble such that the lipid binds to albumin under physiological conditions, and wherein accumulation of the conjugate in the lymph node following administration to a subject in vivo is increased relative to administration of the immunomodulatory compound or molecular adjuvant alone.