title: Prime-boost vaccination with HIV-1 Gag protein and cytosine phosphate guanosine oligodeoxynucleotide, followed by adenovirus, induces sustained and robust humoral and cellular immune responses.
abstract: A prophylactic vaccine for HIV-1 will probably require the induction and maintenance of both humoral and cellular immunity. One current strategy to achieve such long term immune responses is a prime-boost vaccination approach using a DNA priming inoculation, followed by recombinant viral boost. In this report we use a novel prime-boost approach in which the priming injections consist of recombinant HIV-1 Gag protein mixed with cytosine phosphate guanosine oligodeoxynucleotide (CpG ODN), followed by recombinant adenoviral boost expressing HIV-1 Gag. Analysis of the immune responses indicates that HIV-1 Gag protein plus CpG ODN immunization alone induces potent humoral as well as Th1 and CD8+ T cell responses. Boosting with recombinant adenovirus strikingly enhances CD8+, but not Th1, T cell responses, resulting in CD8+ T cell responses far greater in magnitude than Th1 responses. Furthermore, the Th1 and CD8+ T cell responses following prime-boost immunization were seen in both lymphoid and peripheral mucosal organs and were sustained over several months. Together, these data suggest a new immunization approach for elicitation of long term humoral and cellular immune responses.
authors.affiliation: Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Tritel
authors.forename: Amy M
authors.initials: AM
authors.lastname: Stoddard
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Flynn
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Darrah
authors.forename: Chang-you
authors.initials: CY
authors.lastname: Wu
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wille
authors.forename: Javeed A
authors.initials: JA
authors.lastname: Shah
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D007156:Immunologic Memory / Q000235:genetics; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015483:HIV Antibodies; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic