title: Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naïve subjects gives comparable immunogenicity to one dose in ART+ subjects.
abstract: Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1∶12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100,000 copies/ml. Group 2∶12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, haematology and biochemistry. Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. There were no vaccine-related Serious Adverse Events (SAEs) or clinically significant effects on HIV RNA load or CD4 count. In ART naive subjects, the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation, which contracted to baseline by 12 weeks. Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects. Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects; responses were comparable after 2 immunisations. In conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal. A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART. Clinicaltrials.gov trial identifier NCT00731471.
authors.affiliation: Laboratoire de Bacteriolgie-Virologie, Centre Hospitalier Universitaire Le Dantec, Dakar, Senegal.
authors.forename: Tandakha N
authors.initials: TN
authors.lastname: Dieye
authors.forename: Birahim P
authors.initials: BP
authors.lastname: Ndiaye
authors.forename: Alle B
authors.initials: AB
authors.lastname: Dieng
authors.forename: Marema
authors.initials: M
authors.lastname: Fall
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Brittain
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Britain
authors.forename: Samantha
authors.initials: S
authors.lastname: Vermaak
authors.forename: Makhtar
authors.initials: M
authors.lastname: Camara
authors.forename: Halimatou
authors.initials: H
authors.lastname: Diop-Ndiaye
authors.forename: Ndeye Fatou
authors.initials: NF
authors.lastname: Ngom-Gueye
authors.forename: Papa A
authors.initials: PA
authors.lastname: Diaw
authors.forename: Coumba
authors.initials: C
authors.lastname: Toure-Kane
authors.forename: Papa S
authors.initials: PS
authors.lastname: Sow
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma