title: Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles.
abstract: BACKGROUND
  Clade B DNA and recombinant modified vaccinia Ankara (MVA) vaccines producing virus-like particles displaying trimeric membrane-bound envelope glycoprotein (Env) were tested in a phase 2a trial in human immunodeficiency virus (HIV)-uninfected adults for safety, immunogenicity, and 6-month durability of immune responses.
  
  
  METHODS
  A total of 299 individuals received 2 doses of JS7 DNA vaccine and 2 doses of MVA/HIV62B at 0, 2, 4, and 6 months, respectively (the DDMM regimen); 3 doses of MVA/HIV62B at 0, 2, and 6 months (the MMM regimen); or placebo injections.
  
  
  RESULTS
  At peak response, 93.2% of the DDMM group and 98.4% of the MMM group had binding antibodies for Env. These binding antibodies were more frequent and of higher magnitude for the transmembrane subunit (gp41) than the receptor-binding subunit (gp120) of Env. For both regimens, response rates were higher for CD4(+) T cells (66.4% in the DDMM group and 43.1% in the MMM group) than for CD8(+) T cells (21.8% in the DDMM group and 14.9% in the MMM group). Responding CD4(+) and CD8(+) T cells were biased toward Gag, and >70% produced 2 or 3 of the 4 cytokines evaluated (ie, interferon γ, interleukin 2, tumor necrosis factor α, and granzyme B). Six months after vaccination, the magnitudes of antibodies and T-cell responses had decreased by <3-fold.
  
  
  CONCLUSIONS
  DDMM and MMM vaccinations with virus-like particle-expressing immunogens elicited durable antibody and T-cell responses.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Elizaga
authors.affiliation: Laboratory for AIDS Vaccine Research and Development, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Kelly
authors.initials: K
authors.lastname: Seaton
authors.affiliation: Laboratory for AIDS Vaccine Research and Development, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Laboratory for AIDS Vaccine Research and Development, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Alicia
authors.initials: A
authors.lastname: Sato
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center University of Washington, Seattle, Washington.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: DeRosa
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center University of Washington, Seattle, Washington.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Asociacion Civil IMPACTA Salud y Educacion, Lima, Peru.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Lama
authors.affiliation: Asociacion Civil IMPACTA Salud y Educacion, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: Division of Infectious Diseases, Emory University, Atlanta.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Bridge HIV, San Francisco Department of Public Health, California.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.affiliation: Columbia University.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer
authors.affiliation: New York Blood Center, New York, New York.
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.affiliation: Division of AIDS.
authors.forename: Michael
authors.initials: M
authors.lastname: Pensiero
authors.affiliation: Division of AIDS.
authors.forename: Chris
authors.initials: C
authors.lastname: Butler
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.affiliation: GeoVax Inc., Smyrna, Georgia.
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D004337:Drug Carriers; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies; D010919:Placebos; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: DNA; HIV/AIDS; T cells; antibodies; clinical trial; recombinant MVA; vaccines