title: Safety and Immunogenicity of the Recombinant Mycobacterium bovis BCG Vaccine VPM1002 in HIV-Unexposed Newborn Infants in South Africa.
abstract: Tuberculosis is a global threat to which infants are especially vulnerable. Effective vaccines are required to protect infants from this devastating disease. VPM1002, a novel recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine previously shown to be safe and immunogenic in adults, was evaluated for safety in its intended target population, namely, newborn infants in a region with high prevalence of tuberculosis. A total of 48 newborns were vaccinated intradermally with VPM1002 (n = 36) or BCG Danish strain (n = 12) in a phase II open-labeled, randomized trial with a 6-month follow-up period. Clinical and laboratory measures of safety were evaluated during this time. In addition, vaccine-induced immune responses to mycobacteria were analyzed in whole-blood stimulation and proliferation assays. The safety parameters and immunogenicity were comparable in the two groups. Both vaccines induced interleukin-17 (IL-17) responses; however, VPM1002 vaccination led to an increase of CD8+IL-17+T cells at the week 16 and month 6 time points. The incidence of abscess formation was lower for VPM1002 than for BCG. We conclude that VPM1002 is a safe, well-tolerated, and immunogenic vaccine in newborn infants, confirming results from previous trials in adults. These results strongly support further evaluation of the safety and efficacy of this vaccination in larger studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01479972.).
authors.affiliation: SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: André G
authors.initials: AG
authors.lastname: Loxton
authors.affiliation: Vakzine Projekt Management, GmbH, Hanover, Germany.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Knaul
authors.affiliation: Vakzine Projekt Management, GmbH, Hanover, Germany.
authors.forename: Leander
authors.initials: L
authors.lastname: Grode
authors.affiliation: SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gutschmidt
authors.affiliation: Vakzine Projekt Management, GmbH, Hanover, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Meller
authors.affiliation: Vakzine Projekt Management, GmbH, Hanover, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Eisele
authors.affiliation: HJ Clinical Trials Consultancy CC, George, South Africa.
authors.forename: Hilary
authors.initials: H
authors.lastname: Johnstone
authors.affiliation: SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Gian
authors.initials: G
authors.lastname: van der Spuy
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Maertzdorf
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: Stefan H E
authors.initials: SHE
authors.lastname: Kaufmann
authors.affiliation: Desmond Tutu TB Center, Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.affiliation: Fam-Cru, Department of Pediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa mcot@sun.ac.za.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
mesh_terms: D000038:Abscess / Q000453:epidemiology / Q000473:pathology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D013019:South Africa; D016896:Treatment Outcome; D014376:Tuberculosis / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D014614:Vaccines, Synthetic
keywords: HIV-unexposed; IL-17; VPM1002; immunogenicity; newborn; recombinant; recombinant BCG; safety; vaccines; whole blood assay