title: Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity.
abstract: BACKGROUND
  Two parallel studies evaluated safety and immunogenicity of a prophylactic HIV-1 vaccine in 192 HIV-seronegative, low-risk volunteers. Modified vaccinia virus Ankara (MVA) and plasmid DNA (pTHr) expressed HIV-1 clade A gag p24 and p17 fused to a string of 25 overlapping CD8+ T cell epitopes (HIVA).
  
  
  METHODS
  These studies compared intramuscular, subcutaneous, and intradermal MVA at dosage levels ranging from 5x10(6)-2.5x10(8) pfu. In Study IAVI-010, DNA vaccine was given as a prime at months 0 and 1, followed by MVA as a boost at months 5 and 8. In Study IAVI-011, MVA alone was given at months 0 and 2. Regular safety monitoring was performed. Immunogenicity was measured by the interferon (IFN)-gamma ELISPOT assay on peripheral blood mononuclear cells (PBMC).
  
  
  RESULTS
  No serious adverse events were attributed to either vaccine; most adverse events were mild or moderate, although MVA resulted in some severe local reactions. Five vaccine recipients had at least one positive IFN-gamma ELISPOT response, but none were sustained.
  
  
  CONCLUSIONS
  This HIV-1 vaccine candidate was in general safe and well-tolerated. Local reactions were common, but tolerable. Detectable immune responses were infrequent.
authors.affiliation: Kings College London, UK. Barry.Peters@kcl.ac.uk
authors.forename: Barry S
authors.initials: BS
authors.lastname: Peters
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Eftyhia
authors.initials: E
authors.lastname: Vardas
authors.forename: George
authors.initials: G
authors.lastname: Panayotakopoulos
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Mampedi
authors.initials: M
authors.lastname: Bogoshi
authors.forename: Gloria
authors.initials: G
authors.lastname: Omosa-Manyonyi
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Linda
authors.initials: L
authors.lastname: Klavinskis
authors.forename: Bashir
authors.initials: B
authors.lastname: Farah
authors.forename: Tony
authors.initials: T
authors.lastname: Tarragona
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
authors.forename: Andrew
authors.initials: A
authors.lastname: Robinson
authors.forename: Colleen
authors.initials: C
authors.lastname: Pieterse
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.forename: Richard
authors.initials: R
authors.lastname: Thomas
authors.forename: Burc
authors.initials: B
authors.lastname: Barin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: James A
authors.initials: JA
authors.lastname: McIntyre
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
authors.forename: Job
authors.initials: J
authors.lastname: Bwayo
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; C505104:MVA-HIVA vaccine; D019444:Vaccines, DNA; D007371:Interferon-gamma