title: Time course study of the antigen-specific immune response to a PLGA microparticle vaccine formulation.
abstract: Microparticle-based vaccine delivery systems are known to promote enhanced immune responses to protein antigens and can elicit TH1-biased responses when used in combination with Toll-like receptor (TLR) agonists. It is important to understand the kinetics of the immune responses to microparticle-based protein vaccines in order to predict the duration of protective immunity and to optimize prime-boost vaccination regimens. We carried out a 10-week time course study to investigate the magnitude and kinetics of the antibody and cellular immune responses to poly(lactic-co-glycolic acid) (PLGA) microparticles containing 40 μg ovalbumin (OVA) protein and 16 μg CpG-ODN adjuvant (MP/OVA/CpG) in comparison to OVA-containing microparticles, soluble OVA plus CpG, or OVA formulated with Alhydrogel(®) aluminum adjuvant. Mice vaccinated with MP/OVA/CpG developed the highest TH1-associated IgG2b and IgG2c antibody titers, while also eliciting TH2-associated IgG1 antibody titers on par with Alhydrogel(®)-formulated OVA, with all IgG subtype titers peaking at day 56. The MP/OVA/CpG vaccine also induced the highest antigen-specific splenocyte IFN-γ responses, with high levels of IFN-γ responses persisting until day 42. Thus the MP/OVA/CpG formulation produced a sustained and heightened humoral and cellular immune response, with an overall TH1 bias, while maintaining high levels of IgG1 antibody equivalent to that seen with Alhydrogel(®) adjuvant. The time course kinetics study provides a useful baseline for designing vaccination regimens for microparticle-based protein vaccines.
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics (Section of Pediatric Tropical Medicine), Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA.
authors.forename: Melody T
authors.initials: MT
authors.lastname: Tan
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics (Section of Pediatric Tropical Medicine), Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Keegan
authors.affiliation: Medical Scientist Training Program and Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Meagan A
authors.initials: MA
authors.lastname: Barry
authors.affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics (Section of Pediatric Tropical Medicine), Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030, USA; Department of Molecular Virology & Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: michael.heffernan@bcm.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heffernan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D004337:Drug Carriers; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin
keywords: Drug delivery; Immunostimulation; Microsphere; Poly(lactic-co-glycolic acid) (PLGA); Vaccine