Polymeric Nanoparticles as a Self‐Adjuvanting Peptide Vaccine Delivery System: The Role of Shape

Abstract

Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE‐J8 (PJ8), derived from Group A Streptococcus (GAS) M‐protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod‐shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)‐adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption.

Polymeric Nanoparticles as Oral and Intranasal Peptide Vaccine Delivery Systems: The Role of Shape and Conjugation

“…Previously reported serum J8-specific IgG titers following subcutaneous immunizations [ 12 ], and the data reported here from intranasal and oral immunizations, correlated with bactericidal activity against GAS clinical isolates. The relationship between bactericidal activity and serum anti-J8 IgG titers fitted a sigmoidal function, with R 2 = 0.94 against the GAS strain D3840 ( Figure 4 ) and R 2 = 0.88 against GC2203 ( Supporting Information, Figure S7 ).…”

“…As previously reported, the peptide, PJ8 , was synthesized manually using Fmoc-SPPS and derivatized with azide moieties on its N-terminus end [ 12 ]. By employing copper(I)-catalyzed alkyne–azide cycloaddition, azide-functionalized PJ8 was conjugated to alkyne-substituted spheres and tadpoles to produce spheres–PJ8 and tadpoles–PJ8 , respectively ( Figure 1 ).…”

“…By employing copper(I)-catalyzed alkyne–azide cycloaddition, azide-functionalized PJ8 was conjugated to alkyne-substituted spheres and tadpoles to produce spheres–PJ8 and tadpoles–PJ8 , respectively ( Figure 1 ). Worms–PJ8 and rods–PJ8 were produced according to reported protocol [ 12 ]. To confirm the completion of conjugation, the conjugates were assessed via UV-VIS spectroscopy, ninhydrin assay, and IR spectroscopy ( Supporting Information, Figures S1–S3 ).…”

“…Subunit vaccines delivered as nanoparticles are presented to the immune system more effectively, shielded from enzymatic breakdown, and able to elicit immunological responses without the requirement for an adjuvant [ 19 ]. Thus, we recently developed novel self-adjuvant vaccine delivery systems based on polymeric nanoparticles of various shapes, including rods , worms , spheres , and tadpoles [ 12 ]. Delivered subcutaneously, these nanoparticles physically mixed or conjugated with a peptide epitope ( PJ8 ) induced high antibody titers without the need for an adjuvant.…”

“…Here, we propose the use of polymer-based antigen delivery systems to develop a mucosally active GAS vaccine. We recently proved that polymeric nanoparticles built from polystyrene-poly( N -isopropylacrylamide)-poly( N -dimethylacrylamide) can enhance the immunogenicity of peptide antigens following parenteral (subcutaneous) immunization [ 12 ]. However, the ability of these polymers to act as mucosal delivery systems was not examined.…”