title: Resiquimod is a modest adjuvant for HIV-1 gag-based genetic immunization in a mouse model.
abstract: DNA vaccines have been effective at generating useful immune responses in many animal species. However, it is clearly desirable to increase their potency. The identification of adjuvants that increase their cell-mediated immune (CMI) response is therefore an important goal. Resiquimod is an imiquimod analog proven to activate dendritic cells through TLR-7. The adjuvant capacity of resiquimod has not, to our knowledge, been studied in the context of genetic immunization. Here, we studied resiquimod as an adjuvant for plasmid vaccine therapy by intra-muscular immunization of BALB/c mice with HIV-1 gag DNA vaccine without and with several concentrations of resiquimod (ranging from 5-100nM). We observed that resiquimod moderately enhanced IFN-gamma production as measured by a peptide-based ELISPOT assay compared to that obtained in mice immunized with DNA gag only. Antigen-specific T-cell proliferation studies showed a several-fold increase in the stimulation index in mice immunized with DNA gag +50 nM of resiquimod as compared to mice receiving DNA gag alone. Antibody titer also increased, while the antibody isotyping data showed a strong Th1 biased type response. Analysis of cytokine production in serum samples demonstrated a stronger Th1 cytokine bias in the presence of resiquimod. Furthermore, relevant increase in IL-4 production, as measured by ELISPOT assay, was not observed. Our results show that resiquimod can have modest adjuvant activity, in a DNA formulation, driving the immune system towards a cell-mediated immune response. Additional studies involving this adjuvant for DNA vaccines are underway.
authors.affiliation: Department of Pathology, School of Medicine, University of Pennsylvania, 422 Curie Blvd., 505 Stellar-Chance Bldg., Philadelphia, PA 19104-6100, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Calarota
authors.forename: Barbara
authors.initials: B
authors.lastname: Felber
authors.forename: Dominic
authors.initials: D
authors.lastname: Laddy
authors.forename: George
authors.initials: G
authors.lastname: Pavlakis
authors.forename: Jean D
authors.initials: JD
authors.lastname: Boyer
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D015483:HIV Antibodies / Q000032:analysis / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015683:Gene Products, gag; D015483:HIV Antibodies; D007093:Imidazoles; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D007371:Interferon-gamma; C402365:resiquimod