title: Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge.
abstract: There have been encouraging results for the development of an effective HIV vaccine. However, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. We addressed some of these issues by using a simian immunodeficiency virus (SIV) DNA vaccine adjuvanted with plasmid-expressed mucosal chemokines combined with an intravaginal SIV challenge in rhesus macaque (RhM) model. We previously reported on the ability of CCR9 and CCR10 ligand (L) adjuvants to enhance mucosal and systemic IgA and IgG responses in small animals. In this study, RhMs were intramuscularly immunized five times with either DNA or DNA plus chemokine adjuvant delivered by electroporation followed by challenge with SIVsmE660. Sixty-eight percent of all vaccinated animals (P<0.01) remained either uninfected or had aborted infection compared with only 14% in the vaccine naïve group. The highest protection was observed in the CCR10L chemokines group, where six of nine animals had aborted infection and two remained uninfected, leading to 89% protection (P<0.001). The induction of mucosal SIV-specific antibodies and neutralization titers correlated with trends in protection. These results indicate the need to further investigate the contribution of chemokine adjuvants to modulate immune responses and the role of mucosal antibodies in SIV/HIV protection.
authors.affiliation: Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kutzler
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
authors.forename: M C
authors.initials: MC
authors.lastname: Wise
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
authors.forename: N A
authors.initials: NA
authors.lastname: Hutnick
authors.affiliation: Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Moldoveanu
authors.affiliation: Tulane National Primate Research Center and the Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, Covington, Louisiana, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hunter
authors.affiliation: Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: M
authors.initials: M
authors.lastname: Reuter
authors.affiliation: Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
authors.forename: A
authors.initials: A
authors.lastname: Ginsberg
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sylvester
authors.affiliation: Tulane National Primate Research Center and the Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, Covington, Louisiana, USA.
authors.forename: B
authors.initials: B
authors.lastname: Pahar
authors.affiliation: Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: D
authors.initials: D
authors.lastname: Carnathan
authors.affiliation: Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: N
authors.initials: N
authors.lastname: Kathuria
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Khan
authors.affiliation: Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
authors.forename: D
authors.initials: D
authors.lastname: Montefiori
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: N Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Department of Microbiology and Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Betts
authors.affiliation: Department of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mestecky
authors.affiliation: Tulane National Primate Research Center and the Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, Covington, Louisiana, USA.
authors.forename: P
authors.initials: P
authors.lastname: Marx
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, U.S.A.
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D018925:Chemokines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects*; D008024:Ligands; D008253:Macaca mulatta; D010957:Plasmids / Q000737:chemistry / Q000276:immunology; D054388:Receptors, CCR / Q000235:genetics / Q000276:immunology; D054447:Receptors, CCR10 / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000187:drug effects / Q000276:immunology / Q000821:virology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C119309:CC chemokine receptor 9; C515707:Ccr10 protein, mouse; D018925:Chemokines; D008024:Ligands; D054388:Receptors, CCR; D054447:Receptors, CCR10; D019444:Vaccines, DNA