Poly(lactic acid)-poly(ethylene glycol) nanoparticles provide sustained delivery of a Chlamydia trachomatis recombinant MOMP peptide and potentiate systemic adaptive immune responses in mice

Abstract

PLA-PEG [poly(lactic acid)-poly (ethylene glycol)], a biodegradable copolymer, is underexploited for vaccine delivery although it exhibits enhanced biocompatibility and slow release immune-potentiating properties. We document here successful encapsulation of M278, a Chlamydia trachomatis MOMP (major outer-membrane protein) peptide, within PLA-PEG nanoparticles by size (~73-100nm), zeta potential (-16 mV), smooth morphology, encapsulation efficiency (~60%), slow release pattern, and non-toxicity to macrophages. Immunization of mice with encapsulated M278 elicited higher M278-specific T-cell cytokines [Th1 (IFN-γ, IL-2), Th17 (IL-17)] and antibodies [Th1 (IgG2a), Th2 (IgG1, IgG2b)] compared to bare M278. Encapsulated-M278 mouse serum inhibited Chlamydia infectivity of macrophages, with a concomitant transcriptional down-regulation of MOMP, its cognate TLR2 and CD80 co-stimulatory molecule. Collectively, encapsulated M278 potentiated crucial adaptive immune responses, which are required by a vaccine candidate for protective immunity against Chlamydia. Our data highlight PLA-PEG's potential for vaccines, which resides in its slow release and potentiating effects to bolster immune responses.

From the clinical editor: This study highlights the potential of a PLA-PEG-based nanoparticle formulation containing a major outer membrane protein of chlamydia trachomatis in inducing a sustained enhanced immune response, paving the way to the development of a vaccination strategy against this infection.

Keywords: Antibody; Bacteria; Chlamydia trachomatis; Cytokines; PLA–PEG nanoparticles.