Poly-L-lysine-coated nanoparticles are ineffective in inducing mucosal immunity against group a streptococcus

Abstract

Background: Group A Streptococcus (GAS) can cause a range of maladies, from simple throat infections to lethal complication, such as rheumatic heart disease. The M-protein, a bacterial cell surface protein, is the major virulence factor of GAS. Several attempts have been made over the past few decades to develop vaccines against GAS that employed peptides derived from the M-protein. One suchapproach used lipopeptides or lipid core peptide (LCP) systems that incorporated a B cell epitope derived from the conserved region of the M-protein.Methods: In the present study, we prepared different biodegradable polymer [dextran, poly-(lacticcoglycolic- acid) (PLGA), and poly-L-lysine] nanoparticles (NPs)-based delivery systems for a lipopeptide vaccine candidate (LCP-1). The NPs were characterised by their size, charge, morphology, antigen-presenting cells (APCs) uptake and subsequent APCs maturations efficacy, followed by in vivo nasal immunisation in mice.Results: All produced NPs ranged in size from 100-205 nm, and their charge varied depending upon the nature of polymer. A high APCs uptake efficacy for dextran and poly-L-lysine NPs were observed, compared to PLGA NPs. Despite the high uptake by APCs, dextran and poly-L-lysine NPs failed to improve APCs maturation that resulted in low antibody titres. In contrast, while LCP-1 encapsulated into PLGA showed low APCs uptake,it induced significant maturation of DCs and higher antibody titres compared to other NPs.Conclusions: Positively-charged poly-L-lysine NPs were non-immunogenic, while negatively charged PLGA NPs induced similar responses to antigens adjuvanted with cholera toxin B (CTB).