title: Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara.
abstract: Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals.
authors.affiliation: Health Protection Agency, Porton Down, Salisbury, Wiltshire, SP4 0JG, UK. sally.sharpe@hpa.org.uk
authors.forename: Sally
authors.initials: S
authors.lastname: Sharpe
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
authors.forename: Anne
authors.initials: A
authors.lastname: Tinsley-Bown
authors.forename: Mike
authors.initials: M
authors.lastname: Dennis
authors.forename: Stuart
authors.initials: S
authors.lastname: Dowall
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Martin
authors.initials: M
authors.lastname: Cranage
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000285:Administration, Rectal; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004337:Drug Carriers / Q000008:administration & dosage; D004339:Drug Compounding; D006678:HIV / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary; D007413:Intestinal Mucosa / Q000276:immunology*; D019344:Lactic Acid / Q000008:administration & dosage*; D008221:Lymphoid Tissue / Q000276:immunology; D008253:Macaca mulatta; D010865:Pilot Projects; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D011108:Polymers; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid