title: A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults.
abstract: BACKGROUND
  Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses.
  
  
  METHODS
  In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured.
  
  
  RESULTS
  The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration.
  
  
  CONCLUSIONS
  Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01264445.
authors.affiliation: Kenya AIDS Vaccine Initiative, University of Nairobi, Nairobi, Kenya.
authors.forename: Gloria
authors.initials: G
authors.lastname: Omosa-Manyonyi
authors.affiliation: Uganda Virus Research Institute-IAVI, Entebbe, Uganda.
authors.forename: Juliet
authors.initials: J
authors.lastname: Mpendo
authors.affiliation: Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI), Uganda, Research Unit on AIDS, Entebbe, Uganda.
authors.forename: Eugene
authors.initials: E
authors.lastname: Ruzagira
authors.affiliation: Zambia Emory HIV Research Program, Lusaka, Zambia.
authors.forename: William
authors.initials: W
authors.lastname: Kilembe
authors.affiliation: University Teaching Hospital, Lusaka, Zambia.
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Roman
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourguignon
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Alix
authors.initials: A
authors.lastname: Collard
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Dagna
authors.initials: D
authors.lastname: Laufer
authors.affiliation: IAVI, Johannesburg, South Africa.
authors.forename: Gwynn
authors.initials: G
authors.lastname: Stevens
authors.affiliation: IAVI, Human Immunology Laboratory, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.affiliation: IAVI, Human Immunology Laboratory, London, United Kingdom.
authors.forename: Lorna
authors.initials: L
authors.lastname: Clark
authors.affiliation: IAVI, Human Immunology Laboratory, London, United Kingdom.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cormier
authors.affiliation: EMMES Corporation, Rockville, MD, United States of America.
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.affiliation: EMMES Corporation, Rockville, MD, United States of America.
authors.forename: Burc
authors.initials: B
authors.lastname: Barin
authors.affiliation: Global BioSolutions, Melbourne, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Ackland
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Kristen
authors.initials: K
authors.lastname: Syvertsen
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Devika
authors.initials: D
authors.lastname: Zachariah
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Kamaal
authors.initials: K
authors.lastname: Anas
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Eddy
authors.initials: E
authors.lastname: Sayeed
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardo
authors.affiliation: IAVI, Human Immunology Laboratory, London, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: IAVI, Human Immunology Laboratory, London, United Kingdom.
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.affiliation: International AIDS Vaccine Initiative (IAVI), New York, NY, United States of America.
authors.forename: Frances
authors.initials: F
authors.lastname: Priddy
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000276:immunology; D044383:Black People; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D064368:Healthy Volunteers; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D008297:Male; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma