title: Safety and Immunogenicity of a Randomized Phase 1 Prime-Boost Trial With ALVAC-HIV (vCP205) and Oligomeric Glycoprotein 160 From HIV-1 Strains MN and LAI-2 Adjuvanted in Alum or Polyphosphazene.
abstract: Prime-boost regimens comprising ALVAC-HIV (prime) and human immunodeficiency virus type 1 (HIV) Env (boost) induce HIV-specific neutralizing antibody and cell-mediated immune responses, but the impact of boost schedule and adjuvant requires further definition.
  
  
  
  A phase 1 trial was conducted. In part A (open label), 19 volunteers received oligomeric glycoprotein 160 from HIV strains MN and LAI-2 (ogp160 MN/LAI-2) with dose escalation (25, 50, 100 μg) and either polyphosphazene (pP) or alum adjuvant. In part B, 72 volunteers received either placebo (n=12) or recombinant canarypox virus expressing HIV antigens (ALVAC-HIV [vCP205]) with different doses and schedules of ogp160 MN/LAI-2 in pP or alum (n = 60).
  
  
  
  The vaccines were safe and well tolerated, with no vaccine-related serious adverse events. Anti-gp70 V1V2 antibody responses were detected in 17 of 19 part A volunteers (89%) and 10%-100% of part B volunteers. Use of a peripheral blood mononuclear cell-based assay revealed that US-1 primary isolate neutralization was induced in 2 of 19 recipients of ogp160 protein alone (10.5%) and 5 of 49 prime-boost volunteers (10.2%). Among ogp160 recipients, those who received pP were more likely than those who received alum to have serum that neutralized tier 2 viruses (12% vs 0%; P = .015).
  
  
  
  Administration of ogp160 with pP induces primary isolate tier 2 neutralizing antibody responses in a small percentage of volunteers, demonstrating proof of concept and underscoring the importance of further optimization of prime-boost strategies for HIV infection prevention.
  
  
  
  NCT00004579.
authors.affiliation: Department of Retrovirology, US Army Medical Directorate, Armed Forces Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda US Military HIV Research Program.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
authors.affiliation: US Military HIV Research Program.
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.affiliation: US Military HIV Research Program.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
authors.affiliation: International AIDS Vaccine Initiative, New York, New York.
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.affiliation: US Military HIV Research Program.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Jagodzinski
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda US Military HIV Research Program.
authors.forename: Michelle
authors.initials: M
authors.lastname: Liu
authors.affiliation: US Military HIV Research Program.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.affiliation: Consultant, Savannah, Georgia.
authors.forename: John G
authors.initials: JG
authors.lastname: McNeil
authors.affiliation: Sanofi Pasteur, Marcy l'Etoile, France.
authors.forename: Raphaelle
authors.initials: R
authors.lastname: El-Habib
authors.affiliation: US Military HIV Research Program.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Gilliam
authors.affiliation: US Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Robert
authors.initials: R
authors.lastname: Paris
authors.affiliation: Advanced Biosciences Laboratories, Rockville, Maryland.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: VanCott
authors.affiliation: Duke University School of Medicine, Durham, North Carolina.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Office of the Global AIDS Coordinator, Washington D.C.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda US Military HIV Research Program.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: US Military HIV Research Program International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000534:Alum Compounds / Q000008:administration & dosage; D057134:Antibodies, Neutralizing; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015488:HIV Antigens / Q000008:administration & dosage / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D009943:Organophosphorus Compounds; D011108:Polymers; C108974:poly(phosphazene); C041524:aluminum sulfate
keywords: HIV; adjuvant; neutralizing antibody; polyphosphazene; prime-boost; vaccine