title: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Dixit
authors.affiliation: Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA.
authors.forename: Shree R
authors.initials: SR
authors.lastname: Singh
authors.affiliation: Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA; Global Institue of Public Health, New York University, New York, NY, USA.
authors.forename: Abebayehu N
authors.initials: AN
authors.lastname: Yilma
authors.affiliation: Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA; College of Podiatric Medicine, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Agee
authors.affiliation: Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA; Department of Natural Sciences, Albany State University, Albany, GA, USA.
authors.forename: Murtada
authors.initials: M
authors.lastname: Taha
authors.affiliation: Center for NanoBiotechnology Research (CNBR), Alabama State University, Montgomery, AL, USA. Electronic address: vdennis@alasu.edu.
authors.forename: Vida A
authors.initials: VA
authors.lastname: Dennis
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D002692:Chlamydia trachomatis / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D007773:Lactates / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D004337:Drug Carriers; D007773:Lactates; D011994:Recombinant Proteins; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols
keywords: Antibody; Bacteria; Chlamydia trachomatis; Cytokines; PLA–PEG nanoparticles