title: Eliciting cytotoxic T-lymphocyte responses from synthetic vectors containing one or two epitopes in a C57BL/6 mouse model using peptide-containing biodegradable microspheres and adjuvants.
abstract: We describe a vaccine delivery mechanism consisting of a synthetic, non-living vector of large d,l poly(lactic-co-glycolic) acid (PLGA) microspheres that carry specific cytotoxic T lymphocyte (CTL) epitopes. We demonstrate in mice that it can be used to elicit substantial interferon gamma ELISPOT responses to more than one specific epitope in the same individual. Our data suggest that a superior adjuvant configuration for the formulation is to place a TLR-9 agonist CpG inside the microsphere and a TLR-4 agonist MPLA in the injectate solution. This finding contrasts with the observations of others. Our approach provides a means to elicit immune responses efficiently to select epitopes, which may be important for an effective vaccine against HIV.
authors.affiliation: Flow Pharma, Inc., 1900 University Avenue, Suite 200, East Palo Alto, CA 94303, United States; Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States. Electronic address: rrubsamen@partners.org.
authors.forename: R M
authors.initials: RM
authors.lastname: Rubsamen
authors.affiliation: Flow Pharma, Inc., 1900 University Avenue, Suite 200, East Palo Alto, CA 94303, United States.
authors.forename: C V
authors.initials: CV
authors.lastname: Herst
authors.affiliation: Flow Pharma, Inc., 1900 University Avenue, Suite 200, East Palo Alto, CA 94303, United States.
authors.forename: P M
authors.initials: PM
authors.lastname: Lloyd
authors.affiliation: Microsoft Research, 1100 Glendon Ave, PH1, Los Angeles, CA 90024, United States.
authors.forename: D E
authors.initials: DE
authors.lastname: Heckerman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009838:Oligodeoxyribonucleotides; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists; D014612:Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018984:Epitopes, T-Lymphocyte; D009838:Oligodeoxyribonucleotides; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014612:Vaccines; D011100:Polyglycolic Acid
keywords: ELISPOT; Epitope; Mouse; OVA; TLR-4; TLR-9; VSV