title: Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination.
abstract: Priming with the major surface glycoprotein G of respiratory syncytial virus (RSV) expressed by recombinant vaccinia leads to strong Th2 responses and lung eosinophilia during viral challenge. We now show that DNA vaccination in BALB/c mice with plasmids encoding G attenuated RSV replication but also enhanced disease with lung eosinophilia and increased IL-4/5 production. However, formulating the DNA with PLG microparticles reduced the severity of disease during RSV challenge without significantly lessening protection against viral replication. PLG formulation greatly reduced lung eosinophilia and prevented the induction of IL-4 and IL-5 during challenge, accompanied by a less marked CD4+ T cell response and a restoration of the CD8+ T cell recruitment seen during infection of non-vaccinated animals. After RSV challenge, lung eosinophilia was enhanced and prolonged in mice vaccinated with DNA encoding a secreted form of G; this effect was virtually prevented by PLG formulation. Therefore, PLG microparticulate formulation modifies the pattern of immune responses induced by DNA vaccination boosts CD8+ T cell priming and attenuates Th2 responses. We speculate that PLG microparticles affect antigen uptake and processing, thereby influencing the outcome of DNA vaccination.
authors.affiliation: Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College, St. Mary's Campus, Paddington, London W2 1PG, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Helson
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Olszewska
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Jan Zur
authors.initials: JZ
authors.lastname: Megede
authors.forename: Jose A
authors.initials: JA
authors.lastname: Melero
authors.forename: Derek
authors.initials: D
authors.lastname: O'Hagan
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D019344:Lactic Acid / Q000276:immunology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014760:Viral Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication
chemical_list: C502275:G glycoprotein, Respiratory syncytial virus; D015848:Interleukin-5; D011108:Polymers; D022261:Respiratory Syncytial Virus Vaccines; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015847:Interleukin-4; D011100:Polyglycolic Acid; D019344:Lactic Acid