AI Article Synopsis
- - The study examined how Schistosoma mansoni (Sm) infection affects the immune response and safety of the MVA85A tuberculosis vaccine in Ugandan adolescents who have previously received the BCG vaccine. - In a trial with 36 participants (18 with Sm infection and 18 without), the vaccine triggered robust immune responses in both groups without significant differences, and the vaccine was found to be safe with mostly mild side effects. - The findings suggest that the presence of Sm did not hinder T cell responses to the vaccine, although the role of pre-existing antibodies in protection against tuberculosis remains unclear.
Article Abstract
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: ClinicalTrials.gov NCT02178748.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417418 | PMC |
| http://dx.doi.org/10.1371/journal.pntd.0005440 | DOI Listing |
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