The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial

PLoS Negl Trop Dis. 2017 May 4;11(5):e0005440. doi: 10.1371/journal.pntd.0005440. eCollection 2017 May.


Introduction: Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents.

Methods: In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs.

Results: Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly.

Conclusions: The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population.

Trial registration: NCT02178748.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Acyltransferases / immunology*
  • Adolescent
  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology*
  • BCG Vaccine / administration & dosage
  • Child
  • Female
  • Humans
  • Immunity, Cellular
  • Immunogenicity, Vaccine*
  • Immunoglobulin G / blood
  • Linear Models
  • Male
  • Schistosoma mansoni
  • Schistosomiasis mansoni / immunology*
  • T-Lymphocytes / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / immunology*
  • Uganda
  • Vaccination / adverse effects


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • BCG Vaccine
  • Immunoglobulin G
  • MVA 85A
  • Tuberculosis Vaccines
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis

Associated data


Grant support

This work was supported by the European Community's Seventh Framework Programme [FP7/2007-2013] under EC-GA No 241642 and the Wellcome Trust [grant numbers 095778 to AME and 095780/Z/11/Z to HM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.