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.

نویسندگان

  • Barry S Peters
  • Walter Jaoko
  • Eftyhia Vardas
  • George Panayotakopoulos
  • Patricia Fast
  • Claudia Schmidt
  • Jill Gilmour
  • Mampedi Bogoshi
  • Gloria Omosa-Manyonyi
  • Len Dally
  • Linda Klavinskis
  • Bashir Farah
  • Tony Tarragona
  • Pierre-Alexandre Bart
  • Andrew Robinson
  • Colleen Pieterse
  • Wendy Stevens
  • Richard Thomas
  • Burc Barin
  • Andrew J McMichael
  • James A McIntyre
  • Giuseppe Pantaleo
  • Tomás Hanke
  • Job Bwayo
چکیده

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. CONCLUSION This HIV-1 vaccine candidate was in general safe and well-tolerated. Local reactions were common, but tolerable. Detectable immune responses were infrequent.

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عنوان ژورنال:
  • Vaccine

دوره 25 11  شماره 

صفحات  -

تاریخ انتشار 2007