Polyacrylate Dendrimer Nanoparticles: A Self‐Adjuvanting Vaccine Delivery System

Abstract

Special delivery: An effective group A streptococci vaccine is formed from a delivery device consisting of well‐defined dendritic structures with nanoscale dimensions (see picture). The structures are designed to display multiple copies of the minimal B‐cell epitopes, which were in the optimal conformation on the surface of the nanoparticles. The nanoparticles can be administered without the aid of an adjuvant.

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

“…Interestingly, although these polymer-based delivery systems were highly efficient in inducing humoral and cellular immunity after single dose administration, 11,14,16,18 multiple administration of vaccine candidate 4-boost did not significantly improve the efficacy of cellular immune responses. Compounds 6 and 7, which were the constructs possessing both E6/E7 epitopes conjugated to the same polyacrylate dendrimer, produced much weaker anti-tumor activity compared to the physical mixture of two dendritic constructs containing E7 and E6 epitopes (4 + 5 physical mixture).…”

“…11,16 A significant increase in the nitrogen/carbon ratio (N/C) ( Table 2), compared to that of polymer (N/C = 0.004 for L1 (one arm polymer) and S4 (4 arms polymer); N/C = 0.02 for L2 (one arm polymer with two alkyne groups) and D8 (4 arms polymer with 8 alkyne groups)), was apparent, due to the presence of nitrogen-rich peptide in the conjugates. The calculation of the substitution ratio of either E6 43-57 and/or E7 44-57 conjugated to each polymer was based on the comparison of the observed and theoretical N/C ratio for the conjugates, as reported previously.…”

“…and 8 16 (5.8 mg, 0.3 µmol, 1 equiv.) was dissolved in DMF (1 mL), and a copper wire (60 mg) was added.…”

“…14,16 The E7 44-57 azide (10) epitope was conjugated to different polymers via CuAAC "click" reaction to produce polymer-peptide conjugates 1-4.…”

“…11,12,14 tert-Butyl acrylate polymer was chosen as a delivery platform for the vaccine because of its safety profile 15 and ability to serve as a self-adjuvanting moiety to induce both strong humoral and cellular immune responses. [16][17][18] In all of the previous challenge experiments, vaccine candidates were used to treat small tumors, as the vaccines were administered 3 days post tumor implantation. However, ideal therapeutic vaccines should also be able to eradicate large, well-established tumors.…”