title: Synthetic consensus HIV-1 DNA induces potent cellular immune responses and synthesis of granzyme B, perforin in HIV infected individuals.
abstract: This study evaluated the safety and immunogenicity of PENNVAX-B in 12 HIV infected individuals. PENNVAX-B is a combination of three optimized synthetic plasmids encoding for multiclade HIV Gag and Pol and a consensus CladeB Env delivered by electroporation. HIV infected individuals whose virus was effectively suppressed using highly active antiretroviral therapy (HAART) received PENNVAX-B DNA followed by electroporation with CELLECTRA-5P at study weeks 0, 4, 8, and 16. Local administration site and systemic reactions to PENNVAX-B were recorded after each treatment along with any adverse events. Pain of the treatment procedure was assessed using a Visual Analog Scale. Whole PBMCs were isolated for use in IFN ELISpot and Flow Cytometric assays. PENNVAX-B was generally safe and well tolerated. Overall, the four dose regimen was not associated with any serious adverse events or severe local or systemic reactions. A rise in antigen-specific SFU was detected in the INFγ ELISpot assay in all 12 participants. T cells from 8/12 participants loaded with both granzyme B and perforin in response to HIV antigen, an immune finding characteristic of long-term nonprogressors (LTNPs) and elite controllers (ECs). Thus administration of PENNVAX-B may prove useful adjunctive therapy to ART for treatment and control of HIV infection.
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Morrow
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ramirez
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Slager
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Kraynyak
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Malissa
authors.initials: M
authors.lastname: Diehl
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Shah
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Khan
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lee
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Boyer
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
authors.affiliation: Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bagarazzi
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016384:Consensus Sequence; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D053804:Granzymes / Q000096:biosynthesis* / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis* / Q000235:genetics; D014611:Vaccination; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes