title: A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults.
abstract: BACKGROUND
  Strategies to enhance the immunogenicity of DNA vaccines in humans include i) co-administration of molecular adjuvants, ii) intramuscular administration followed by in vivo electroporation (IM/EP) and/or iii) boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.
  
  
  METHODS
  Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG) plasmid DNA (pDNA) vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12) (GENEVAX IL-12) given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.
  
  
  RESULTS
  All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs) were reported. T cell and antibody response rates after HIVMAG (x3) prime-Ad35 (x1) boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ) ELISPOT responses was highest after HIVMAG (x3) without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS) were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3) prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.
  
  
  CONCLUSIONS
  The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01496989.
authors.affiliation: Uganda Virus Research Institute-IAVI, Entebbe, Uganda.
authors.forename: Juliet
authors.initials: J
authors.lastname: Mpendo
authors.affiliation: Kenya AIDS Vaccine Initiative, University of Nairobi, Nairobi, Kenya.
authors.forename: Gaudensia
authors.initials: G
authors.lastname: Mutua
authors.affiliation: Projet San Francisco (PSF), Kigali, Rwanda.
authors.forename: Julien
authors.initials: J
authors.lastname: Nyombayire
authors.affiliation: Projet San Francisco (PSF), Kigali, Rwanda.
authors.forename: Rosine
authors.initials: R
authors.lastname: Ingabire
authors.affiliation: Uganda Virus Research Institute-IAVI, Entebbe, Uganda.
authors.forename: Annet
authors.initials: A
authors.lastname: Nanvubya
authors.affiliation: Kenya AIDS Vaccine Initiative, University of Nairobi, Nairobi, Kenya.
authors.forename: Omu
authors.initials: O
authors.lastname: Anzala
authors.affiliation: Projet San Francisco (PSF), Kigali, Rwanda.
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.affiliation: IAVI, Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.affiliation: IAVI, Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kopycinski
authors.affiliation: EMMES Corporation, Rockville, Maryland, United States of America.
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.affiliation: ICHOR Medical Systems, Inc., San Diego, California, United States of America.
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.affiliation: Profectus BioSciences, Inc., Tarrytown, New York, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
authors.affiliation: Profectus BioSciences, Inc., Tarrytown, New York, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, New York, United States of America.
authors.forename: Kristen
authors.initials: K
authors.lastname: Syvertsen
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, New York, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lehrman
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, New York, United States of America.
authors.forename: Beth
authors.initials: B
authors.lastname: Rasmussen
authors.affiliation: IAVI, Human Immunology Laboratory, Imperial College, London, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, New York, United States of America.
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, New York, United States of America.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Fast
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, New York, United States of America.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology; D000256:Adenoviridae / Q000378:metabolism; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000009:adverse effects* / Q000276:immunology*; D003710:Demography; D004311:Double-Blind Method; D018274:Electroporation; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D004279:DNA, Viral; D015483:HIV Antibodies; D010919:Placebos; D018664:Interleukin-12; D007371:Interferon-gamma