title: Antigen-specific humoral and cellular immune responses can be modulated in rhesus macaques through the use of IFN-gamma, IL-12, or IL-18 gene adjuvants.
abstract: DNA or nucleic acid immunization has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. Moreover, immune responses induced by DNA immunization can be enhanced and modulated by the use of molecular adjuvants. To engineer the immune response in vivo towards more T-helper (Th)1-type cellular responses, we investigated the co-delivery of inteferon (IFN)-gamma, interleukin (IL)-12, and IL-18 genes along with DNA vaccine constructs. We observed that both antigen-specific humoral and cellular immune responses can be modulated through the use of cytokine adjuvants in mice. Most of this work has been performed in rodent models. There has been little confirmation of this technology in primates. We also evaluated the immunomodulatory effects of this approach in rhesus macaques, since non-human primates represent the most relevant animal models for human immunodeficiency virus (HIV) vaccine studies. As in the murine studies, we also observed that each Th1 cytokine adjuvant distinctively regulated the level of immune responses generated. Co-immunization of IFN-gamma and IL-18 in macaques enhanced the level of antigen-specific antibody responses. Similarly, co-delivery of IL-12 and IL-18 also enhanced the level of antigen-specific Th proliferative responses. These results extend this adjuvant strategy in a more relevant primate model and support the potential utility of these molecular adjuvants in DNA vaccine regimens.
authors.affiliation: Department of Pathology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: L K
authors.initials: LK
authors.lastname: Nottingham
authors.forename: A
authors.initials: A
authors.lastname: Tsai
authors.forename: D J
authors.initials: DJ
authors.lastname: Lee
authors.forename: H C
authors.initials: HC
authors.lastname: Maguire
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.forename: T
authors.initials: T
authors.lastname: Dentchev
authors.forename: K H
authors.initials: KH
authors.lastname: Manson
authors.forename: M S
authors.initials: MS
authors.lastname: Wyand
authors.forename: M G
authors.initials: MG
authors.lastname: Agadjanyan
authors.forename: K E
authors.initials: KE
authors.lastname: Ugen
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000662:veterinary; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D020382:Interleukin-18; D019444:Vaccines, DNA; D018664:Interleukin-12