title: Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults: a phase I clinical trial.
abstract: The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770.
authors.affiliation: Jenner Institute; University of Oxford, Oxford, UK.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Rowland
authors.forename: Ansar A
authors.initials: AA
authors.lastname: Pathan
authors.forename: Iman
authors.initials: I
authors.lastname: Satti
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.forename: Magali M L
authors.initials: MM
authors.lastname: Matsumiya
authors.forename: Megan
authors.initials: M
authors.lastname: Whittaker
authors.forename: Angela M
authors.initials: AM
authors.lastname: Minassian
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: O'Hara
authors.forename: Matthew
authors.initials: M
authors.lastname: Hamill
authors.forename: Janet T
authors.initials: JT
authors.lastname: Scott
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Harris
authors.forename: Hazel C
authors.initials: HC
authors.lastname: Poyntz
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bateman
authors.forename: Joel
authors.initials: J
authors.lastname: Meyer
authors.forename: Nicola
authors.initials: N
authors.lastname: Williams
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods*; D019444:Vaccines, DNA; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; C549320:MVA 85A; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines
keywords: heterologous prime-boost regimes; phase I clinical trial; poxvirus-vectored subunit vaccines; tuberculosis vaccines