title: Phase I clinical trial safety of DNA- and modified virus Ankara-vectored human immunodeficiency virus type 1 (HIV-1) vaccines administered alone and in a prime-boost regime to healthy HIV-1-uninfected volunteers.
abstract: DNA- and modified virus Ankara (MVA)-vectored candidate vaccines expressing human immunodeficiency virus type 1 (HIV-1) clade A-derived p24/p17 gag fused to a string of HLA class I epitopes, called HIVA, were tested in phase I trials in healthy, HIV-1/2-uninfected adults in Oxford, United Kingdom. Eighteen volunteers were vaccinated with pTHr.HIVA DNA (IAVI-001) alone, 8 volunteers received MVA.HIVA (IAVI-003) alone and 9 volunteers from study IAVI-001 were boosted with MVA.HIVA 9-14 months after DNA priming (IAVI-005). Immunogenicity results observed in these trials was published previously [Mwau M, Cebere I, Sutton J, Chikoti P, Winstone N, Wee EG-T, et al. An HIV-1 clade A vaccine in clinical trials: stimulation of HIV-specific T cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J Gen Virol 2004;85:911-9]. Here, we report on the safety of the two vaccines and the vaccine regimes. Overall, both candidate vaccines were safe and well tolerated. There were no reported vaccine-related adverse events over the 6-month period of the study and up to 2 years after the last vaccination. There were no moderate or severe local symptoms recorded after the pTHr.HIVA DNA intramuscular administration. Almost all participants experienced local reactogenicity events such as redness and induration after MVA.HIVA intradermal injection. Thus, the results from these initial small phase I trials administering the pTHr.HIVA DNA and MVA.HIVA vaccines either alone or in a prime-boost regime to healthy HIV-1/2-negative adults indicated that the vaccines were safe and warranted further testing of this approach in larger phase I/II studies.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
authors.forename: Inese
authors.initials: I
authors.lastname: Cebere
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Alison
authors.initials: A
authors.lastname: Simmons
authors.forename: Sheena
authors.initials: S
authors.lastname: McCormack
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Carol
authors.initials: C
authors.lastname: Smith
authors.forename: Mary
authors.initials: M
authors.lastname: Brooks
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Roberts
authors.forename: Simon C
authors.initials: SC
authors.lastname: Darwin
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Fast
authors.forename: Christopher
authors.initials: C
authors.lastname: Conlon
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D015195:Drug Design; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006805:Human Experimentation; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary; D016037:Single-Blind Method; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA