title: A novel HIV vaccine adjuvanted by IC31 induces robust and persistent humoral and cellular immunity.
abstract: The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses.
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Laura
authors: L
authors: Pattacini
authors: Gregory J
authors: GJ
authors: Mize
authors: Jessica B
authors: JB
authors: Graham
authors: Tayler R
authors: TR
authors: Fluharty
authors: Tisha M
authors: TM
authors: Graham
authors: Karen
authors: K
authors: Lingnau
authors: Benjamin
authors: B
authors: Wizel
authors: Beatriz
authors: B
authors: Perdiguero
authors: Mariano
authors: M
authors: Esteban
authors: Giuseppe
authors: G
authors: Pantaleo
authors: Mingchao
authors: M
authors: Shen
authors: Gregory A
authors: GA
authors: Spies
authors: M Juliana
authors: MJ
authors: McElrath
authors: Jennifer M
authors: JM
authors: Lund
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004338:Drug Combinations; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology*; D056724:Immunity, Humoral / Q000187:drug effects* / Q000276:immunology*; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D008643:Mesentery / Q000276:immunology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D004338:Drug Combinations; D015699:HIV Envelope Protein gp120; C544002:IC31 adjuvant; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D054299:env Gene Products, Human Immunodeficiency Virus; C514793:gp120 protein, Human immunodeficiency virus 1; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C041524:aluminum sulfate